Surfactant Protein D in Respiratory and Non-Respiratory Diseases

Grith L Sorensen, Grith L Sorensen

Abstract

Surfactant protein D (SP-D) is a multimeric collectin that is involved in innate immune defense and expressed in pulmonary, as well as non-pulmonary, epithelia. SP-D exerts antimicrobial effects and dampens inflammation through direct microbial interactions and modulation of host cell responses via a series of cellular receptors. However, low protein concentrations, genetic variation, biochemical modification, and proteolytic breakdown can induce decomposition of multimeric SP-D into low-molecular weight forms, which may induce pro-inflammatory SP-D signaling. Multimeric SP-D can decompose into trimeric SP-D, and this process, and total SP-D levels, are partly determined by variation within the SP-D gene, SFTPD. SP-D has been implicated in the development of respiratory diseases including respiratory distress syndrome, bronchopulmonary dysplasia, allergic asthma, and chronic obstructive pulmonary disease. Disease-induced breakdown or modifications of SP-D facilitate its systemic leakage from the lung, and circulatory SP-D is a promising biomarker for lung injury. Moreover, studies in preclinical animal models have demonstrated that local pulmonary treatment with recombinant SP-D is beneficial in these diseases. In recent years, SP-D has been shown to exert antimicrobial and anti-inflammatory effects in various non-pulmonary organs and to have effects on lipid metabolism and pro-inflammatory effects in vessel walls, which enhance the risk of atherosclerosis. A common SFTPD polymorphism is associated with atherosclerosis and diabetes, and SP-D has been associated with metabolic disorders because of its effects in the endothelium and adipocytes and its obesity-dampening properties. This review summarizes and discusses the reported genetic associations of SP-D with disease and the clinical utility of circulating SP-D for respiratory disease prognosis. Moreover, basic research on the mechanistic links between SP-D and respiratory, cardiovascular, and metabolic diseases is summarized. Perspectives on the development of SP-D therapy are addressed.

Keywords: allergic asthma; atherosclerosis; chronic obstructive lung disease; respiratory distress syndrome; surfactant protein D.

Figures

Figure 1
Figure 1
Multimerization of surfactant protein D (SP-D). (A) Regions of the trimeric SP-D subunit. The subunit structure has been drawn to the approximate dimensions of the protein domains. Adapted with permission from Ref. (190). (B) Multimerization of the trimeric SP-D subunit (3 chains) into 4-subunit cruciform (12 chains) or fuzziball >4-subunit (>12 chains) structures of SP-D. (C) Schematic overview of how multimeric SP-D is implicated in antimicrobial defense. Binding of multimeric SP-D to microbe-associated glycans may block interaction of the microbe with its receptors, aggregate the microbes, or SP-D may act as an opsonin, enhancing endocytic uptake of the microbe in host cells. Only fuzziball SP-D multimers are shown for simplicity. CTLD, C-type lectin domain.
Figure 2
Figure 2
Circulatory spill-over of pulmonary surfactant protein D (SP-D) in inflammatory disease. SP-D is synthesized by Club cells, type II alveolar cells, and endothelial cells, and the levels of SP-D multimers and trimers in the serum are highly genetically determined. In the inflamed lung, the production of trimeric SP-D is increased, due to various chemical modifications and proteolytic breakdown of the protein, and loss of air–blood barrier integrity allows spill-over of pulmonary SP-D into the circulation. For simplicity, only alveolar damage is illustrated. Moreover, only fuzziball SP-D multimers are depicted.
Figure 3
Figure 3
Surfactant protein D (SP-D)-mediated effects in experimental allergic asthma. The overview of cellular functions in allergic asthma was inspired by Lambrecht and Hammad (347) and Fahy (357). The multiple effects of SP-D include (1) removal of allergens by induction of aggregation and accelerating their binding and uptake by alveolar macrophages (92, 154, 358); (2) suppression of M2 macrophage polarization and allergen-stimulated macrophage NO production (123, 352); (3) inhibition of IgE binding to allergens, blocking allergen-induced histamine release by basophils and degranulation by mast cells (153, 154); (4) suppression of peripheral blood mononuclear cell interleukin (IL)-2 secretion (146), lymphocyte proliferation (358), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4)-dependent induction of apoptosis (145). SP-D-mediated T-cell responses are CTLA4 dependent (149); (5) decreased lymphocyte IL-4 and IL-13 release (221); (6) suppression of eosinophil chemotaxis and degranulation, and induction of apoptosis (142, 143); (7) SP-D increases allergen interaction with respiratory epithelium, yet dampens epithelial chemotactic signaling (161); (8) SP-D increases uptake and removal of allergens in macrophages (93); (9) the overall effects of SP-D in allergic asthma in vivo include dampening of eosinophilia, alveolar macrophage accumulation, increased specific antibody levels, airway hyperreactivity, subepithelial fibrosis, and mucous metaplasia. These are features, which have either been observed in Sftpd−/− mice or that are subjected to phenotype rescue by endogenous SP-D, or administration of recombinant SP-D/60-kDa recombinant trimeric fragment of SP-D lacking the N-terminal but retaining a part of the collagen region (, , , , , , , –353, 359). Leakage of pulmonary SP-D to the circulation in allergic asthma has been demonstrated in clinical samples (19). Only trimeric SP-D and fuzziball SP-D multimers are shown for simplicity.
Figure 4
Figure 4
Surfactant protein D (SP-D)-mediated effects in experimental pulmonary inflammation and airspace enlargement in chronic obstructive pulmonary disease (COPD). The overview of cellular functions in COPD was inspired by Barnes (408) and Brusselle et al. (407). Multiple effects of endogenous or exogenous SP-D include (1) suppression of inflammation elicited by noxious stimuli (395, 400, 402, 409). The SP-D-mediated mechanisms includes SP-Ds interaction with immune-regulatory receptors (117, 134, 170, 174, 177), depression of oxidative stress, including iNOS activity, protection of phospholipid oxidation (, –413); (2) decrease of macrophage transforming growth factor-β (TGF-β) production and fibrocyte recruitment (163). These SP-D effects may partly enable suppression of age-induced influences; (3) increased septal wall thickening by fibrotic deposition (194, 397); (4) airspace enlargement and loss of surface area of alveolar epithelia (194, 202, 397, 414); (5) suppression of the production of ROS and NO by macrophages, and possibly additional cell types (125, 194, 395, 409, 411). Fibrotic and emphysematic changes in the lung may also depend on inhibition of iNOS by SP-D (397, 413). (5/6) SP-D suppresses metalloproteinase production in alveolar macrophages (125, 194) and putatively additional cell types. The result is an overall decrease in pulmonary protease activity via oxidant-sensitive pathways (125, 194); (7) prolonged alveolar epithelial cell and macrophage survival after cigarette smoke extract exposure or oxidative stress (276, 410); (8) increased efferocytosis (94, 121, 170, 201, 415); (9) opsonization of microbes for phagocytosis (91). (10) The resulting effects of SP-D relevant for COPD-like phenotypes in vivo include dampening of chronic low-level pulmonary inflammation predominantly mediated by macrophages and correlated with reduced oxidative stress and protease activity (125, 194), which can prevent changes in pulmonary elastance due to both tissue breakdown and fibrotic build up that occur sequentially with increasing age and exposure to noxious stimuli (395, 397, 409, 413). Leakage of pulmonary SP-D to the circulation in COPD has been demonstrated using clinical samples (280). Only trimeric SP-D and fuzziball SP-D multimers are shown for simplicity.
Figure 5
Figure 5
Surfactant protein D (SP-D)-mediated effects in atherogenesis. The simplified overview of cellular functions in atherogenesis was inspired by Skaggs et al. (458). Effects of SP-D in a long-term diet-induced model of atherosclerosis include (1) repression of high-density lipoprotein (HDL)-cholesterol levels (48) and also additional plasma lipid levels in a genetic model (457); (2) model-dependent induction of tumor necrosis factor-α (TNF-α) in vivo (48, 457) and TNF-α induction in monocytes in vitro, dependent on osteoclast-associated receptor (OSCAR) signaling (133); (3) induction of macrophage proliferation (457); (4) induction of circulating monocytes; (5) decreased coverage of smooth muscle in plaques (457); (6) the result is an overall increase in atherosclerotic plaque formation with accumulation of foam cells and cholesterol crystals, accompanied by disturbed plasma lipid levels in Sftpd−/− mice compared with Sftpd+/+ mice (48, 457). Moreover, TNF-α and NO increase endothelial SP-D expression (63) and circulating SP-D is increased in clinical cardiovascular disease (CVD) (25, 429). Only trimeric SP-D and fuzziball SP-D multimers are shown for simplicity.

References

    1. Holmskov U, Thiel S, Jensenius JC. Collections and ficolins: humoral lectins of the innate immune defense. Annu Rev Immunol (2003) 21:547–78.10.1146/annurev.immunol.21.120601.140954
    1. Ohtani K, Suzuki Y, Eda S, Kawai T, Kase T, Yamazaki H, et al. Molecular cloning of a novel human collectin from liver (CL-L1). J Biol Chem (1999) 274:13681–9.10.1074/jbc.274.19.13681
    1. Nakamura K, Funakoshi H, Miyamoto K, Tokunaga F, Nakamura T. Molecular cloning and functional characterization of a human scavenger receptor with C-type lectin (SRCL), a novel member of a scavenger receptor family. Biochem Biophys Res Commun (2001) 280:1028–35.10.1006/bbrc.2000.4210
    1. Keshi H, Sakamoto T, Kawai T, Ohtani K, Katoh T, Jang SJ, et al. Identification and characterization of a novel human collectin CL-K1. Microbiol Immunol (2006) 50:1001–13.10.1111/j.1348-0421.2006.tb03868.x
    1. Henriksen ML, Brandt J, Andrieu JP, Nielsen C, Jensen PH, Holmskov U, et al. Heteromeric complexes of native collectin kidney 1 and collectin liver 1 are found in the circulation with MASPs and activate the complement system. J Immunol (2013) 191:6117–27.10.4049/jimmunol.1302121
    1. Ohtani K, Suzuki Y, Eda S, Kawai T, Kase T, Keshi H, et al. The membrane-type collectin CL-P1 is a scavenger receptor on vascular endothelial cells. J Biol Chem (2001) 276:44222–8.10.1074/jbc.M103942200
    1. Ma YJ, Hein E, Munthe-Fog L, Skjoedt MO, Bayarri-Olmos R, Romani L, et al. Soluble collectin-12 (CL-12) is a pattern recognition molecule initiating complement activation via the alternative pathway. J Immunol (2015) 195:3365–73.10.4049/jimmunol.1500493
    1. Wright JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol (2005) 5:58–68.10.1038/nri1528
    1. Madsen J, Kliem A, Tornoe I, Skjodt K, Koch C, Holmskov U. Localization of lung surfactant protein D on mucosal surfaces in human tissues. J Immunol (2000) 164:5866–70.10.4049/jimmunol.164.11.5866
    1. Stahlman MT, Gray ME, Hull WM, Whitsett JA. Immunolocalization of surfactant protein-D (SP-D) in human fetal, newborn, and adult tissues. J Histochem Cytochem (2002) 50:651–60.10.1177/002215540205000506
    1. Kankavi O. Immunodetection of surfactant proteins in human organ of corti, eustachian tube and kidney. Acta Biochim Pol (2003) 50:1057–64.
    1. Woodworth BA, Lathers D, Neal JG, Skinner M, Richardson M, Young MR, et al. Immunolocalization of surfactant protein A and D in sinonasal mucosa. Am J Rhinol (2006) 20:461–5.10.2500/ajr.2006.20.2892
    1. Schicht M, Knipping S, Hirt R, Beileke S, Sel S, Paulsen F, et al. Detection of surfactant proteins A, B, C, and D in human nasal mucosa and their regulation in chronic rhinosinusitis with polyps. Am J Rhinol Allergy (2013) 27:24–9.10.2500/ajra.2013.27.3838
    1. Woodworth BA, Neal JG, Newton D, Joseph K, Kaplan AP, Baatz JE, et al. Surfactant protein A and D in human sinus mucosa: a preliminary report. ORL J Otorhinolaryngol Relat Spec (2007) 69:57–60.10.1159/000096718
    1. Honda Y, Kuroki Y, Matsuura E, Nagae H, Takahashi H, Akino T, et al. Pulmonary surfactant protein D in sera and bronchoalveolar lavage fluids. Am J Respir Crit Care Med (1995) 152:1860–6.10.1164/ajrccm.152.6.8520747
    1. Sorensen GL, Husby S, Holmskov U. Surfactant protein A and surfactant protein D variation in pulmonary disease. Immunobiology (2007) 212:381–416.10.1016/j.imbio.2007.01.003
    1. Crouch E, Persson A, Chang D. Accumulation of surfactant protein D in human pulmonary alveolar proteinosis. Am J Pathol (1993) 142:241–8.
    1. Kotecha S, Doull I, Davies P, McKenzie Z, Madsen J, Clark HW, et al. Functional heterogeneity of pulmonary surfactant protein-D in cystic fibrosis. Biochim Biophys Acta (2013) 1832:2391–400.10.1016/j.bbadis.2013.10.002
    1. Mackay RA, Grainge CL, Lau LC, Barber C, Clark HW, Howarth PH. Airway surfactant protein D (SP-D) deficiency in adults with severe asthma. Chest (2016) 149(5):1165–72.10.1016/j.chest.2015.11.012
    1. Hohwy T, Otkjaer K, Madsen J, Soerensen G, Nielsen O, Vestergaard C, et al. Surfactant protein D in atopic dermatitis and psoriasis. Exp Dermatol (2006) 15:168–74.10.1111/j.1600-0625.2006.00406.x
    1. Mo YK, Kankavi O, Masci PP, Mellick GD, Whitehouse MW, Boyle GM, et al. Surfactant protein expression in human skin: evidence and implications. J Invest Dermatol (2007) 127:381–6.10.1038/sj.jid.5700561
    1. Brauer L, Moschter S, Beileke S, Jager K, Garreis F, Paulsen FP. Human parotid and submandibular glands express and secrete surfactant proteins A, B, C and D. Histochem Cell Biol (2009) 132:331–8.10.1007/s00418-009-0609-x
    1. Schicht M, Stengl C, Sel S, Heinemann F, Gotz W, Petschelt A, et al. The distribution of human surfactant proteins within the oral cavity and their role during infectious diseases of the gingiva. Ann Anat (2015) 199:92–7.10.1016/j.aanat.2014.05.040
    1. Saka R, Yanagihara I, Sasaki T, Nose S, Takeuchi M, Nakayama M, et al. Immunolocalization of surfactant protein D in the liver from infants with cholestatic liver disease. J Pediatr Surg (2015) 50:297–300.10.1016/j.jpedsurg.2014.11.020
    1. Hu F, Liang W, Ren Z, Wang G, Ding G. Surfactant protein D inhibits lipopolysaccharide-induced monocyte chemoattractant protein-1 expression in human renal tubular epithelial cells: implication for tubulointerstitial fibrosis. Clin Exp Immunol (2012) 167:514–22.10.1111/j.1365-2249.2011.04521.x
    1. Kurimura Y, Nishitani C, Ariki S, Saito A, Hasegawa Y, Takahashi M, et al. Surfactant protein D inhibits adherence of uropathogenic Escherichia coli to the bladder epithelial cells and the bacterium-induced cytotoxicity: a possible function in urinary tract. J Biol Chem (2012) 287:39578–88.10.1074/jbc.M112.380287
    1. Oberley RE, Goss KL, Ault KA, Crouch EC, Snyder JM. Surfactant protein D is present in the human female reproductive tract and inhibits Chlamydia trachomatis infection. Mol Hum Reprod (2004) 10:861–70.10.1093/molehr/gah117
    1. Leth-Larsen R, Floridon C, Nielsen O, Holmskov U. Surfactant protein D in the female genital tract. Mol Hum Reprod (2004) 10:149–54.10.1093/molehr/gah022
    1. Yadav AK, Chaudhari H, Warke H, Shah PK, Dodagatta-Marri E, Kishore U, et al. Differential expression of collectins in human placenta and role in inflammation during spontaneous labor. PLoS One (2014) 9:e108815.10.1371/journal.pone.0108815
    1. Miyamura K, Malhotra R, Hoppe HJ, Reid KB, Phizackerley PJ, Macpherson P, et al. Surfactant proteins A (SP-A) and D (SP-D): levels in human amniotic fluid and localization in the fetal membranes. Biochim Biophys Acta (1994) 1210:303–7.10.1016/0005-2760(94)90233-X
    1. Madhukaran SP, Kishore U, Jamil K, Choolani M, Lu J. Decidual expression and localization of human surfactant protein SP-A and SP-D, and complement protein C1q. Mol Immunol (2015) 66:197–207.10.1016/j.molimm.2015.03.001
    1. Sati L, Seval-Celik Y, Demir R. Lung surfactant proteins in the early human placenta. Histochem Cell Biol (2010) 133:85–93.10.1007/s00418-009-0642-9
    1. Lu J, Willis AC, Reid KB. Purification, characterization and cDNA cloning of human lung surfactant protein D. Biochem J (1992) 284:795–802.10.1042/bj2840795
    1. Mason RJ, Nielsen LD, Kuroki Y, Matsuura E, Freed JH, Shannon JM. A 50-kDa variant form of human surfactant protein D. Eur Respir J (1998) 12:1147–55.10.1183/09031936.98.12051147
    1. Inoue T, Matsuura E, Nagata A, Ogasawara Y, Hattori A, Kuroki Y, et al. Enzyme-linked immunosorbent assay for human pulmonary surfactant protein D. J Immunol Methods (1994) 173:157–64.10.1016/0022-1759(94)90295-X
    1. Sorensen GL, Hoegh SV, Leth-Larsen R, Thomsen TH, Floridon C, Smith K, et al. Multimeric and trimeric subunit SP-D are interconvertible structures with distinct ligand interaction. Mol Immunol (2009) 46:3060–9.10.1016/j.molimm.2009.06.005
    1. Leth-Larsen R, Garred P, Jensenius H, Meschi J, Hartshorn K, Madsen J, et al. A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D. J Immunol (2005) 174:1532–8.10.4049/jimmunol.174.3.1532
    1. Rokade S, Madan T. Testicular expression of SP-A, SP-D and MBL-A is positively regulated by testosterone and modulated by lipopolysaccharide. Immunobiology (2016) 221(9):975–85.10.1016/j.imbio.2016.05.005
    1. Beileke S, Claassen H, Wagner W, Matthies C, Ruf C, Hartmann A, et al. Expression and localization of lung surfactant proteins in human testis. PLoS One (2015) 10:e0143058.10.1371/journal.pone.0143058
    1. Oberley RE, Goss KL, Dahmoush L, Ault KA, Crouch EC, Snyder JM. A role for surfactant protein D in innate immunity of the human prostate. Prostate (2005) 65:241–51.10.1002/pros.20292
    1. Schob S, Schicht M, Sel S, Stiller D, Kekule AS, Paulsen F, et al. The detection of surfactant proteins A, B, C and D in the human brain and their regulation in cerebral infarction, autoimmune conditions and infections of the CNS. PLoS One (2013) 8:e74412.10.1371/journal.pone.0074412
    1. Schob S, Lobsien D, Friedrich B, Bernhard MK, Gebauer C, Dieckow J, et al. The cerebral surfactant system and its alteration in hydrocephalic conditions. PLoS One (2016) 11:e0160680.10.1371/journal.pone.0160680
    1. Brauer L, Kindler C, Jager K, Sel S, Nolle B, Pleyer U, et al. Detection of surfactant proteins A and D in human tear fluid and the human lacrimal system. Invest Ophthalmol Vis Sci (2007) 48:3945–53.10.1167/iovs.07-0201
    1. Wu X, Zhao G, Lin J, Jiang N, Li C, Hu L, et al. The production mechanism and immunosuppression effect of pulmonary surfactant protein D via toll like receptor 4 signaling pathway in human corneal epithelial cells during Aspergillus fumigatus infection. Int Immunopharmacol (2015) 29:433–9.10.1016/j.intimp.2015.10.018
    1. Ni M, Evans DJ, Hawgood S, Anders EM, Sack RA, Fleiszig SM. Surfactant protein D is present in human tear fluid and the cornea and inhibits epithelial cell invasion by Pseudomonas aeruginosa. Infect Immun (2005) 73:2147–56.10.1128/IAI.73.4.2147-2156.2005
    1. Che CY, Jia WY, Xu Q, Li N, Hu LT, Jiang N, et al. The roles of surfactant protein D during Aspergillus fumigatus infection in human corneal epithelial cells. Int J Ophthalmol (2012) 5:13–7.10.3980/j.issn.2222-3959.2012.01.03
    1. Snyder GD, Oberley-Deegan RE, Goss KL, Romig-Martin SA, Stoll LL, Snyder JM, et al. Surfactant protein D is expressed and modulates inflammatory responses in human coronary artery smooth muscle cells. Am J Physiol Heart Circ Physiol (2008) 294:H2053–9.10.1152/ajpheart.91529.2007
    1. Sorensen GL, Madsen J, Kejling K, Tornoe I, Nielsen O, Townsend P, et al. Surfactant protein D is proatherogenic in mice. Am J Physiol Heart Circ Physiol (2006) 290:H2286–94.10.1152/ajpheart.01105.2005
    1. Lambertsen KL, Ostergaard K, Clausen BH, Hansen S, Stenvang J, Thorsen SB, et al. No effect of ablation of surfactant protein-D on acute cerebral infarction in mice. J Neuroinflammation (2014) 11:123.10.1186/1742-2094-11-123
    1. Christensen AF, Sorensen GL, Junker K, Revald PH, Varnum C, Sorensen FB, et al. Localization of surfactant protein-D in the rheumatoid synovial membrane. APMIS (2017) 126(1):9–13.10.1111/apm.12785
    1. Ortega FJ, Pueyo N, Moreno-Navarrete JM, Sabater M, Rodriguez-Hermosa JI, Ricart W, et al. The lung innate immune gene surfactant protein-D is expressed in adipose tissue and linked to obesity status. Int J Obes (Lond) (2013) 37:1532–8.10.1038/ijo.2013.23
    1. Bourbon JR, Chailley-Heu B. Surfactant proteins in the digestive tract, mesentery, and other organs: evolutionary significance. Comp Biochem Physiol A Mol Integr Physiol (2001) 129:151–61.10.1016/S1095-6433(01)00312-9
    1. Voorhout WF, Veenendaal T, Kuroki Y, Ogasawara Y, van Golde LM, Geuze HJ. Immunocytochemical localization of surfactant protein D (SP-D) in type II cells, Clara cells, and alveolar macrophages of rat lung. J Histochem Cytochem (1992) 40:1589–97.10.1177/40.10.1527377
    1. Dulkerian SJ, Gonzales LW, Ning Y, Ballard PL. Regulation of surfactant protein D in human fetal lung. Am J Respir Cell Mol Biol (1996) 15:781–6.10.1165/ajrcmb.15.6.8969273
    1. Rust K, Bingle L, Mariencheck W, Persson A, Crouch EC. Characterization of the human surfactant protein D promoter: transcriptional regulation of SP-D gene expression by glucocorticoids. Am J Respir Cell Mol Biol (1996) 14:121–30.10.1165/ajrcmb.14.2.8630261
    1. He Y, Crouch EC, Rust K, Spaite E, Brody SL. Proximal promoter of the surfactant protein D gene: regulatory roles of AP-1, forkhead box, and GT box binding proteins. J Biol Chem (2000) 275:31051–60.10.1074/jbc.M003499200
    1. Besnard V, Wert SE, Kaestner KH, Whitsett JA. Stage-specific regulation of respiratory epithelial cell differentiation by Foxa1. Am J Physiol Lung Cell Mol Physiol (2005) 289:L750–9.10.1152/ajplung.00151.2005
    1. He Y, Crouch E. Surfactant protein D gene regulation. Interactions among the conserved CCAAT/enhancer-binding protein elements. J Biol Chem (2002) 277:19530–7.10.1074/jbc.M201126200
    1. Charles A, Tang X, Crouch E, Brody JS, Xiao ZX. Retinoblastoma protein complexes with C/EBP proteins and activates C/EBP-mediated transcription. J Cell Biochem (2001) 83:414–25.10.1002/jcb.1239
    1. Dave V, Childs T, Whitsett JA. Nuclear factor of activated T cells regulates transcription of the surfactant protein D gene (Sftpd) via direct interaction with thyroid transcription factor-1 in lung epithelial cells. J Biol Chem (2004) 279:34578–88.10.1074/jbc.M404296200
    1. Ni M, Tam C, Verma A, Ramphal R, Hawgood S, Evans DJ, et al. Expression of surfactant protein D in human corneal epithelial cells is upregulated by Pseudomonas aeruginosa. FEMS Immunol Med Microbiol (2008) 54:177–84.10.1111/j.1574-695X.2008.00461.x
    1. Kamio K, Usuki J, Azuma A, Matsuda K, Ishii T, Inomata M, et al. Nintedanib modulates surfactant protein-D expression in A549 human lung epithelial cells via the c-Jun N-terminal kinase-activator protein-1 pathway. Pulm Pharmacol Ther (2015) 32:29–36.10.1016/j.pupt.2015.03.001
    1. Lee MY, Sorensen GL, Holmskov U, Vanhoutte PM. The presence and activity of SP-D in porcine coronary endothelial cells depend on Akt/PI(3)K, Erk and nitric oxide and decrease after multiple passaging. Mol Immunol (2008) 46(6):1050–7.10.1016/j.molimm.2008.09.027
    1. Lin Z, Floros J. Heterogeneous allele expression of pulmonary SP-D gene in rat large intestine and other tissues. Physiol Genomics (2002) 11:235–43.10.1152/physiolgenomics.00061.2002
    1. Dahl M, Juvonen PO, Holmskov U, Husby S. Surfactant protein D in newborn infants: factors influencing surfactant protein D levels in umbilical cord blood and capillary blood. Pediatr Res (2005) 58:908–12.10.1203/
    1. Deterding RR, Shimizu H, Fisher JH, Shannon JM. Regulation of surfactant protein D expression by glucocorticoids in vitro and in vivo. Am J Respir Cell Mol Biol (1994) 10:30–7.10.1165/ajrcmb.10.1.8292379
    1. Crouch E, Rust K, Marienchek W, Parghi D, Chang D, Persson A. Developmental expression of pulmonary surfactant protein D (SP-D). Am J Respir Cell Mol Biol (1991) 5:13–8.10.1165/ajrcmb/5.1.13
    1. Ogasawara Y, Kuroki Y, Tsuzuki A, Ueda S, Misaki H, Akino T. Pre- and postnatal stimulation of pulmonary surfactant protein D by in vivo dexamethasone treatment of rats. Life Sci (1992) 50:1761–7.10.1016/0024-3205(92)90059-X
    1. Wong CJ, Akiyama J, Allen L, Hawgood S. Localization and developmental expression of surfactant proteins D and A in the respiratory tract of the mouse. Pediatr Res (1996) 39:930–7.10.1203/00006450-199606000-00002
    1. Wang JY, Yeh TF, Lin YC, Miyamura K, Holmskov U, Reid KB. Measurement of pulmonary status and surfactant protein levels during dexamethasone treatment of neonatal respiratory distress syndrome. Thorax (1996) 51:907–13.10.1136/thx.51.9.907
    1. Mariencheck W, Crouch E. Modulation of surfactant protein D expression by glucocorticoids in fetal rat lung. Am J Respir Cell Mol Biol (1994) 10:419–29.10.1165/ajrcmb.10.4.8136157
    1. Schmiedl A, Grutzner D, Hoffmann T, von Horsten S, Stephan M. DPP4 inhibitors increase differentially the expression of surfactant proteins in Fischer 344 rats. Acta Physiol (Oxf) (2014) 212:248–61.10.1111/apha.12350
    1. Aderibigbe AO, Thomas RF, Mercer RR, Auten RL, Jr. Brief exposure to 95% oxygen alters surfactant protein D and mRNA in adult rat alveolar and bronchiolar epithelium. Am J Respir Cell Mol Biol (1999) 20:219–27.10.1165/ajrcmb.20.2.3348
    1. Jain-Vora S, LeVine AM, Chroneos Z, Ross GF, Hull WM, Whitsett JA. Interleukin-4 enhances pulmonary clearance of Pseudomonas aeruginosa. Infect Immun (1998) 66:4229–36.
    1. Ikegami M, Whitsett JA, Chroneos ZC, Ross GF, Reed JA, Bachurski CJ, et al. IL-4 increases surfactant and regulates metabolism in vivo. Am J Physiol Lung Cell Mol Physiol (2000) 278:L75–80.10.1152/ajplung.2000.278.1.L75
    1. Homer RJ, Zheng T, Chupp G, He S, Zhu Z, Chen Q, et al. Pulmonary type II cell hypertrophy and pulmonary lipoproteinosis are features of chronic IL-13 exposure. Am J Physiol Lung Cell Mol Physiol (2002) 283:L52–9.10.1152/ajplung.00438.2001
    1. Fujita M, Shannon JM, Ouchi H, Voelker DR, Nakanishi Y, Mason RJ. Serum surfactant protein D is increased in acute and chronic inflammation in mice. Cytokine (2005) 31:25–33.10.1016/j.cyto.2005.02.006
    1. Rucka Z, Vanhara P, Koutna I, Tesarova L, Potesilova M, Stejskal S, et al. Differential effects of insulin and dexamethasone on pulmonary surfactant-associated genes and proteins in A549 and H441 cells and lung tissue. Int J Mol Med (2013) 32:211–8.10.3892/ijmm.2013.1363
    1. Oberley RE, Goss KL, Hoffmann DS, Ault KA, Neff TL, Ramsey KH, et al. Regulation of surfactant protein D in the mouse female reproductive tract in vivo. Mol Hum Reprod (2007) 13:863–8.10.1093/molehr/gam074
    1. Kay S, Metkari SM, Madan T. Ovarian hormones regulate SP-D expression in the mouse uterus during estrous cycle and early pregnancy. Am J Reprod Immunol (2015) 74:77–88.10.1111/aji.12369
    1. Oberley RE, Goss KL, Quintar AA, Maldonado CA, Snyder JM. Regulation of surfactant protein D in the rodent prostate. Reprod Biol Endocrinol (2007) 5:42.10.1186/1477-7827-5-42
    1. Gravholt CH, Leth-Larsen R, Lauridsen AL, Thiel S, Hansen TK, Holmskov U, et al. The effects of GH and hormone replacement therapy on serum concentrations of mannan-binding lectin, surfactant protein D and vitamin D binding protein in Turner syndrome. Eur J Endocrinol (2004) 150:355–62.10.1530/eje.0.1500355
    1. Pikaar JC, Voorhout WF, van Golde LM, Verhoef J, Van Strijp JA, van Iwaarden JF. Opsonic activities of surfactant proteins A and D in phagocytosis of Gram-negative bacteria by alveolar macrophages. J Infect Dis (1995) 172:481–9.10.1093/infdis/172.2.481
    1. Madan T, Eggleton P, Kishore U, Strong P, Aggrawal SS, Sarma PU, et al. Binding of pulmonary surfactant proteins A and D to Aspergillus fumigatus conidia enhances phagocytosis and killing by human neutrophils and alveolar macrophages. Infect Immun (1997) 65:3171–9.
    1. Hartshorn KL, Crouch E, White MR, Colamussi ML, Kakkanatt A, Tauber B, et al. Pulmonary surfactant proteins A and D enhance neutrophil uptake of bacteria. Am J Physiol (1998) 274:L958–69.
    1. Restrepo CI, Dong Q, Savov J, Mariencheck WI, Wright JR. Surfactant protein D stimulates phagocytosis of Pseudomonas aeruginosa by alveolar macrophages. Am J Respir Cell Mol Biol (1999) 21:576–85.10.1165/ajrcmb.21.5.3334
    1. Ofek I, Mesika A, Kalina M, Keisari Y, Podschun R, Sahly H, et al. Surfactant protein D enhances phagocytosis and killing of unencapsulated phase variants of Klebsiella pneumoniae. Infect Immun (2001) 69:24–33.10.1128/IAI.69.1.24-33.2001
    1. LeVine AM, Elliott J, Whitsett JA, Srikiatkhachorn A, Crouch E, DeSilva N, et al. Surfactant protein-d enhances phagocytosis and pulmonary clearance of respiratory syncytial virus. Am J Respir Cell Mol Biol (2004) 31:193–9.10.1165/rcmb.2003-0107OC
    1. Tecle T, White MR, Sorensen G, Gantz D, Kacak N, Holmskov U, et al. Critical role for cross-linking of trimeric lectin domains of surfactant protein D in antiviral activity against influenza A virus. Biochem J (2008) 412:323–9.10.1042/BJ20071663
    1. Thawer S, Auret J, Schnoeller C, Chetty A, Smith K, Darby M, et al. Surfactant protein-D is essential for immunity to helminth infection. PLoS Pathog (2016) 12:e1005461.10.1371/journal.ppat.1005461
    1. Nayak A, Dodagatta-Marri E, Tsolaki AG, Kishore U. An insight into the diverse roles of surfactant proteins, SP-A and SP-D in innate and adaptive immunity. Front Immunol (2012) 3:131.10.3389/fimmu.2012.00131
    1. Erpenbeck VJ, Malherbe DC, Sommer S, Schmiedl A, Steinhilber W, Ghio AJ, et al. Surfactant protein D increases phagocytosis and aggregation of pollen-allergen starch granules. Am J Physiol Lung Cell Mol Physiol (2005) 288:L692–8.10.1152/ajplung.00362.2004
    1. Winkler C, Huper K, Wedekind AC, Rochlitzer S, Hartwig C, Muller M, et al. Surfactant protein D modulates pulmonary clearance of pollen starch granules. Exp Lung Res (2010) 36:522–30.10.3109/01902141003790148
    1. Palaniyar N, Clark H, Nadesalingam J, Hawgood S, Reid KB. Surfactant protein D binds genomic DNA and apoptotic cells, and enhances their clearance, in vivo. Ann N Y Acad Sci (2003) 1010:471–5.10.1196/annals.1299.085
    1. Kendall M, Ding P, Mackay RM, Deb R, McKenzie Z, Kendall K, et al. Surfactant protein D (SP-D) alters cellular uptake of particles and nanoparticles. Nanotoxicology (2013) 7:963–73.10.3109/17435390.2012.689880
    1. Sarashina-Kida H, Negishi H, Nishio J, Suda W, Nakajima Y, Yasui-Kato M, et al. Gallbladder-derived surfactant protein D regulates gut commensal bacteria for maintaining intestinal homeostasis. Proc Natl Acad Sci U S A (2017) 114:10178–83.10.1073/pnas.1712837114
    1. Barfod KK, Roggenbuck M, Al-Shuweli S, Fakih D, Sorensen SJ, Sorensen GL. Alterations of the murine gut microbiome in allergic airway disease are independent of surfactant protein D. Heliyon (2017) 3:e00262.10.1016/j.heliyon.2017.e00262
    1. Crouch EC, Smith K, McDonald B, Briner D, Linders B, McDonald J, et al. Species differences in the carbohydrate binding preferences of surfactant protein D. Am J Respir Cell Mol Biol (2006) 35:84–94.10.1165/rcmb.2005-0462OC
    1. Jakel A, Qaseem AS, Kishore U, Sim RB. Ligands and receptors of lung surfactant proteins SP-A and SP-D. Front Biosci (Landmark Ed) (2013) 18:1129–40.10.2741/4168
    1. Hartshorn K, Chang D, Rust K, White M, Heuser J, Crouch E. Interactions of recombinant human pulmonary surfactant protein D and SP-D multimers with influenza A. Am J Physiol (1996) 271:L753–62.
    1. Jounblat R, Kadioglu A, Iannelli F, Pozzi G, Eggleton P, Andrew PW. Binding and agglutination of Streptococcus pneumoniae by human surfactant protein D (SP-D) vary between strains, but SP-D fails to enhance killing by neutrophils. Infect Immun (2004) 72:709–16.10.1128/IAI.72.2.709-716.2004
    1. Hartshorn KL, White MR, Crouch EC. Contributions of the N- and C-terminal domains of surfactant protein d to the binding, aggregation, and phagocytic uptake of bacteria. Infect Immun (2002) 70:6129–39.10.1128/IAI.70.11.6129-6139.2002
    1. Douda DN, Jackson R, Grasemann H, Palaniyar N. Innate immune collectin surfactant protein D simultaneously binds both neutrophil extracellular traps and carbohydrate ligands and promotes bacterial trapping. J Immunol (2011) 187:1856–65.10.4049/jimmunol.1004201
    1. Wu H, Kuzmenko A, Wan S, Schaffer L, Weiss A, Fisher JH, et al. Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability. J Clin Invest (2003) 111:1589–602.10.1172/JCI16889
    1. Kuzmenko AI, Wu H, McCormack FX. Pulmonary collectins selectively permeabilize model bacterial membranes containing rough lipopolysaccharide. Biochemistry (2006) 45:2679–85.10.1021/bi0522652
    1. McCormack FX, Gibbons R, Ward SR, Kuzmenko A, Wu H, Deepe GS, Jr. Macrophage-independent fungicidal action of the pulmonary collectins. J Biol Chem (2003) 278:36250–6.10.1074/jbc.M303086200
    1. Meschi J, Crouch EC, Skolnik P, Yahya K, Holmskov U, Leth-Larsen R, et al. Surfactant protein D binds to human immunodeficiency virus (HIV) envelope protein gp120 and inhibits HIV replication. J Gen Virol (2005) 86:3097–107.10.1099/vir.0.80764-0
    1. Hartshorn KL, White MR, Tecle T, Tornoe I, Sorensen GL, Crouch EC, et al. Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D. Respir Res (2007) 8:9.10.1186/1465-9921-8-9
    1. Goh BC, Rynkiewicz MJ, Cafarella TR, White MR, Hartshorn KL, Allen K, et al. Molecular mechanisms of inhibition of influenza by surfactant protein D revealed by large-scale molecular dynamics simulation. Biochemistry (2013) 52:8527–38.10.1021/bi4010683
    1. Fakih D, Pilecki B, Schlosser A, Jepsen CS, Thomsen LK, Ormhoj M, et al. Protective effects of surfactant protein D treatment in 1,3-beta-glucan-modulated allergic inflammation. Am J Physiol Lung Cell Mol Physiol (2015) 309:L1333–43.10.1152/ajplung.00090.2015
    1. Geunes-Boyer S, Oliver TN, Janbon G, Lodge JK, Heitman J, Perfect JR, et al. Surfactant protein D increases phagocytosis of hypocapsular Cryptococcus neoformans by murine macrophages and enhances fungal survival. Infect Immun (2009) 77:2783–94.10.1128/IAI.00088-09
    1. Holmer SM, Evans KS, Asfaw YG, Saini D, Schell WA, Ledford JG, et al. Impact of surfactant protein D, interleukin-5, and eosinophilia on cryptococcosis. Infect Immun (2014) 82:683–93.10.1128/IAI.00855-13
    1. Yong SJ, Vuk-Pavlovic Z, Standing JE, Crouch EC, Limper AH. Surfactant protein D-mediated aggregation of Pneumocystis carinii impairs phagocytosis by alveolar macrophages. Infect Immun (2003) 71:1662–71.10.1128/IAI.71.4.1662-1671.2003
    1. Ferguson JS, Voelker DR, McCormack FX, Schlesinger LS. Surfactant protein D binds to Mycobacterium tuberculosis bacilli and lipoarabinomannan via carbohydrate-lectin interactions resulting in reduced phagocytosis of the bacteria by macrophages. J Immunol (1999) 163:312–21.
    1. Ferguson JS, Voelker DR, Ufnar JA, Dawson AJ, Schlesinger LS. Surfactant protein D inhibition of human macrophage uptake of Mycobacterium tuberculosis is independent of bacterial agglutination. J Immunol (2002) 168:1309–14.10.4049/jimmunol.168.3.1309
    1. Lemos MP, McKinney J, Rhee KY. Dispensability of surfactant proteins A and D in immune control of Mycobacterium tuberculosis infection following aerosol challenge of mice. Infect Immun (2011) 79:1077–85.10.1128/IAI.00286-10
    1. Liu CF, Rivere M, Huang HJ, Puzo G, Wang JY. Surfactant protein D inhibits mite-induced alveolar macrophage and dendritic cell activations through TLR signalling and DC-SIGN expression. Clin Exp Allergy (2010) 40:111–22.10.1111/j.1365-2222.2009.03367.x
    1. Yamazoe M, Nishitani C, Takahashi M, Katoh T, Ariki S, Shimizu T, et al. Pulmonary surfactant protein D inhibits lipopolysaccharide (LPS)-induced inflammatory cell responses by altering LPS binding to its receptors. J Biol Chem (2008) 283:35878–88.10.1074/jbc.M807268200
    1. Janssen WJ, McPhillips KA, Dickinson MG, Linderman DJ, Morimoto K, Xiao YQ, et al. Surfactant proteins A and D suppress alveolar macrophage phagocytosis via interaction with SIRP alpha. Am J Respir Crit Care Med (2008) 178:158–67.10.1164/rccm.200711-1661OC
    1. Yamaguchi R, Sakamoto A, Yamamoto T, Ishimaru Y, Narahara S, Sugiuchi H, et al. Surfactant protein D inhibits interleukin-12p40 production by macrophages through the SIRPalpha/ROCK/ERK signaling pathway. Am J Med Sci (2017) 353:559–67.10.1016/j.amjms.2017.03.013
    1. Litvack ML, Djiadeu P, Renganathan SD, Sy S, Post M, Palaniyar N. Natural IgM and innate immune collectin SP-D bind to late apoptotic cells and enhance their clearance by alveolar macrophages in vivo. Mol Immunol (2010) 48:37–47.10.1016/j.molimm.2010.09.014
    1. Atochina-Vasserman EN, Bates SR, Zhang P, Abramova H, Zhang Z, Gonzales L, et al. Early alveolar epithelial dysfunction promotes lung inflammation in a mouse model of Hermansky-Pudlak syndrome. Am J Respir Crit Care Med (2011) 184:449–58.10.1164/rccm.201011-1882OC
    1. Takeda K, Miyahara N, Rha YH, Taube C, Yang ES, Joetham A, et al. Surfactant protein D regulates airway function and allergic inflammation through modulation of macrophage function. Am J Respir Crit Care Med (2003) 168:783–9.10.1164/rccm.200304-548OC
    1. Douda DN, Farmakovski N, Dell S, Grasemann H, Palaniyar N. SP-D counteracts GM-CSF-mediated increase of granuloma formation by alveolar macrophages in lysinuric protein intolerance. Orphanet J Rare Dis (2009) 4:29.10.1186/1750-1172-4-29
    1. Yoshida M, Korfhagen TR, Whitsett JA. Surfactant protein D regulates NF-kappaB and matrix metalloproteinase production in alveolar macrophages via oxidant-sensitive pathways. J Immunol (2001) 166:7514–9.10.4049/jimmunol.166.12.7514
    1. Tino MJ, Wright JR. Surfactant proteins A and D specifically stimulate directed actin-based responses in alveolar macrophages. Am J Physiol (1999) 276:L164–74.
    1. Trask BC, Malone MJ, Lum EH, Welgus HG, Crouch EC, Shapiro SD. Induction of macrophage matrix metalloproteinase biosynthesis by surfactant protein D. J Biol Chem (2001) 276:37846–52.10.1074/jbc.M102524200
    1. Keisari Y, Wang H, Mesika A, Matatov R, Nissimov L, Crouch E, et al. Surfactant protein D-coated Klebsiella pneumoniae stimulates cytokine production in mononuclear phagocytes. J Leukoc Biol (2001) 70:135–41.
    1. Kudo K, Sano H, Takahashi H, Kuronuma K, Yokota S, Fujii N, et al. Pulmonary collectins enhance phagocytosis of Mycobacterium avium through increased activity of mannose receptor. J Immunol (2004) 172:7592–602.10.4049/jimmunol.172.12.7592
    1. Palaniyar N, Clark H, Nadesalingam J, Shih MJ, Hawgood S, Reid KB. Innate immune collectin surfactant protein D enhances the clearance of DNA by macrophages and minimizes anti-DNA antibody generation. J Immunol (2005) 174:7352–8.10.4049/jimmunol.174.11.7352
    1. Liu CF, Chen YL, Chang WT, Shieh CC, Yu CK, Reid KB, et al. Mite allergen induces nitric oxide production in alveolar macrophage cell lines via CD14/toll-like receptor 4, and is inhibited by surfactant protein D. Clin Exp Allergy (2005) 35:1615–24.10.1111/j.1365-2222.2005.02387.x
    1. Atochina-Vasserman EN, Abramova EV, Tomer Y, Scott P, Nazarov VA, Kruglov SV, et al. SP-D-dependent regulation of NO metabolism in lipopolysaccharide-stimulated peritoneal macrophages. Bull Exp Biol Med (2009) 147:415–20.10.1007/s10517-009-0525-z
    1. Barrow AD, Palarasah Y, Bugatti M, Holehouse AS, Byers DE, Holtzman MJ, et al. OSCAR is a receptor for surfactant protein D that activates TNF-alpha release from human CCR2+ inflammatory monocytes. J Immunol (2015) 194:3317–26.10.4049/jimmunol.1402289
    1. Ge MQ, Kokalari B, Flayer CH, Killingbeck SS, Redai IG, MacFarlane AW, IV, et al. Cutting edge: role of NK cells and surfactant protein D in dendritic cell lymph node homing: effects of ozone exposure. J Immunol (2016) 196:553–7.10.4049/jimmunol.1403042
    1. Crouch EC, Persson A, Griffin GL, Chang D, Senior RM. Interactions of pulmonary surfactant protein D (SP-D) with human blood leukocytes. Am J Respir Cell Mol Biol (1995) 12:410–5.10.1165/ajrcmb.12.4.7695920
    1. Bufler P, Schmidt B, Schikor D, Bauernfeind A, Crouch EC, Griese M. Surfactant protein A and D differently regulate the immune response to nonmucoid Pseudomonas aeruginosa and its lipopolysaccharide. Am J Respir Cell Mol Biol (2003) 28:249–56.10.1165/rcmb.4896
    1. Pandit H, Gopal S, Sonawani A, Yadav AK, Qaseem AS, Warke H, et al. Surfactant protein D inhibits HIV-1 infection of target cells via interference with gp120-CD4 interaction and modulates pro-inflammatory cytokine production. PLoS One (2014) 9:e102395.10.1371/journal.pone.0102395
    1. Hartshorn KL, Crouch EC, White MR, Eggleton P, Tauber AI, Chang D, et al. Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses. J Clin Invest (1994) 94:311–9.10.1172/JCI117323
    1. Hartshorn KL, Reid KB, White MR, Jensenius JC, Morris SM, Tauber AI, et al. Neutrophil deactivation by influenza A viruses: mechanisms of protection after viral opsonization with collectins and hemagglutination-inhibiting antibodies. Blood (1996) 87:3450–61.
    1. White MR, Crouch E, Vesona J, Tacken PJ, Batenburg JJ, Leth-Larsen R, et al. Respiratory innate immune proteins differentially modulate the neutrophil respiratory burst response to influenza A virus. Am J Physiol Lung Cell Mol Physiol (2005) 289:L606–16.10.1152/ajplung.00130.2005
    1. White M, Kingma P, Tecle T, Kacak N, Linders B, Heuser J, et al. Multimerization of surfactant protein D, but not its collagen domain, is required for antiviral and opsonic activities related to influenza virus. J Immunol (2008) 181:7936–43.10.4049/jimmunol.181.11.7936
    1. von Bredow C, Hartl D, Schmid K, Schabaz F, Brack E, Reinhardt D, et al. Surfactant protein D regulates chemotaxis and degranulation of human eosinophils. Clin Exp Allergy (2006) 36:1566–74.10.1111/j.1365-2222.2006.02598.x
    1. Mahajan L, Madan T, Kamal N, Singh VK, Sim RB, Telang SD, et al. Recombinant surfactant protein-D selectively increases apoptosis in eosinophils of allergic asthmatics and enhances uptake of apoptotic eosinophils by macrophages. Int Immunol (2008) 20:993–1007.10.1093/intimm/dxn058
    1. Ogawa H, Ledford JG, Mukherjee S, Aono Y, Nishioka Y, Lee JJ, et al. Surfactant protein D attenuates sub-epithelial fibrosis in allergic airways disease through TGF-beta. Respir Res (2014) 15:143.10.1186/s12931-014-0143-9
    1. Pandit H, Thakur G, Koippallil Gopalakrishnan AR, Dodagatta-Marri E, Patil A, Kishore U, et al. Surfactant protein D induces immune quiescence and apoptosis of mitogen-activated peripheral blood mononuclear cells. Immunobiology (2016) 221:310–22.10.1016/j.imbio.2015.10.004
    1. Borron PJ, Crouch EC, Lewis JF, Wright JR, Possmayer F, Fraher LJ. Recombinant rat surfactant-associated protein D inhibits human T lymphocyte proliferation and IL-2 production. J Immunol (1998) 161:4599–603.
    1. Borron PJ, Mostaghel EA, Doyle C, Walsh ES, McHeyzer-Williams MG, Wright JR. Pulmonary surfactant proteins A and D directly suppress CD3+/CD4+ cell function: evidence for two shared mechanisms. J Immunol (2002) 169:5844–50.10.4049/jimmunol.169.10.5844
    1. Fisher JH, Larson J, Cool C, Dow SW. Lymphocyte activation in the lungs of SP-D null mice. Am J Respir Cell Mol Biol (2002) 27:24–33.10.1165/ajrcmb.27.1.4563
    1. Lin KW, Jen KY, Suarez CJ, Crouch EC, Perkins DL, Finn PW. Surfactant protein D-mediated decrease of allergen-induced inflammation is dependent upon CTLA4. J Immunol (2010) 184:6343–9.10.4049/jimmunol.0901947
    1. Madsen J, Gaiha GD, Palaniyar N, Dong T, Mitchell DA, Clark HW. Surfactant protein D modulates HIV infection of both T-cells and dendritic cells. PLoS One (2013) 8:e59047.10.1371/journal.pone.0059047
    1. Djiadeu P, Kotra LP, Sweezey N, Palaniyar N. Surfactant protein D delays Fas- and TRAIL-mediated extrinsic pathway of apoptosis in T cells. Apoptosis (2017) 22:730–40.10.1007/s10495-017-1348-4
    1. Djiadeu P, Farmakovski N, Azzouz D, Kotra LP, Sweezey N, Palaniyar N. Surfactant protein D regulates caspase-8-mediated cascade of the intrinsic pathway of apoptosis while promoting bleb formation. Mol Immunol (2017) 92:190–8.10.1016/j.molimm.2017.10.016
    1. Madan T, Kishore U, Shah A, Eggleton P, Strong P, Wang JY, et al. Lung surfactant proteins A and D can inhibit specific IgE binding to the allergens of Aspergillus fumigatus and block allergen-induced histamine release from human basophils. Clin Exp Immunol (1997) 110:241–9.10.1111/j.1365-2249.1997.tb08323.x
    1. Malherbe DC, Erpenbeck VJ, Abraham SN, Crouch EC, Hohlfeld JM, Wright JR. Surfactant protein D decreases pollen-induced IgE-dependent mast cell degranulation. Am J Physiol Lung Cell Mol Physiol (2005) 289:L856–66.10.1152/ajplung.00009.2005
    1. Brinker KG, Martin E, Borron P, Mostaghel E, Doyle C, Harding CV, et al. Surfactant protein D enhances bacterial antigen presentation by bone marrow-derived dendritic cells. Am J Physiol Lung Cell Mol Physiol (2001) 281:L1453–63.10.1152/ajplung.2001.281.6.L1453
    1. Hansen S, Lo B, Evans K, Neophytou P, Holmskov U, Wright JR. Surfactant protein D augments bacterial association but attenuates major histocompatibility complex class II presentation of bacterial antigens. Am J Respir Cell Mol Biol (2007) 36:94–102.10.1165/rcmb.2006-0195OC
    1. Hortobagyi L, Kierstein S, Krytska K, Zhu X, Das AM, Poulain F, et al. Surfactant protein D inhibits TNF-alpha production by macrophages and dendritic cells in mice. J Allergy Clin Immunol (2008) 122:521–8.10.1016/j.jaci.2008.05.002
    1. Hasegawa Y, Takahashi M, Ariki S, Asakawa D, Tajiri M, Wada Y, et al. Surfactant protein D suppresses lung cancer progression by downregulation of epidermal growth factor signaling. Oncogene (2015) 34:838–45.10.1038/onc.2014.20
    1. Yang Z, Jaeckisch SM, Mitchell CG. Enhanced binding of Aspergillus fumigatus spores to A549 epithelial cells and extracellular matrix proteins by a component from the spore surface and inhibition by rat lung lavage fluid. Thorax (2000) 55:579–84.10.1136/thorax.55.7.579
    1. Schleh C, Erpenbeck VJ, Winkler C, Lauenstein HD, Nassimi M, Braun A, et al. Allergen particle binding by human primary bronchial epithelial cells is modulated by surfactant protein D. Respir Res (2010) 11:83.10.1186/1465-9921-11-83
    1. Schleh C, Rothen-Rutishauser BM, Blank F, Lauenstein HD, Nassimi M, Krug N, et al. Surfactant protein D modulates allergen particle uptake and inflammatory response in a human epithelial airway model. Respir Res (2012) 13:8.10.1186/1465-9921-13-8
    1. McKenzie Z, Kendall M, Mackay RM, Tetley TD, Morgan C, Griffiths M, et al. Nanoparticles modulate surfactant protein A and D mediated protection against influenza A infection in vitro. Philos Trans R Soc Lond B Biol Sci (2015) 370:20140049.10.1098/rstb.2014.0049
    1. Aono Y, Ledford JG, Mukherjee S, Ogawa H, Nishioka Y, Sone S, et al. Surfactant protein-D regulates effector cell function and fibrotic lung remodeling in response to bleomycin injury. Am J Respir Crit Care Med (2012) 185:525–36.10.1164/rccm.201103-0561OC
    1. Sano H, Chiba H, Iwaki D, Sohma H, Voelker DR, Kuroki Y. Surfactant proteins A and D bind CD14 by different mechanisms. J Biol Chem (2000) 275:22442–51.10.1074/jbc.M001107200
    1. Ohya M, Nishitani C, Sano H, Yamada C, Mitsuzawa H, Shimizu T, et al. Human pulmonary surfactant protein D binds the extracellular domains of toll-like receptors 2 and 4 through the carbohydrate recognition domain by a mechanism different from its binding to phosphatidylinositol and lipopolysaccharide. Biochemistry (2006) 45:8657–64.10.1021/bi060176z
    1. Nie X, Nishitani C, Yamazoe M, Ariki S, Takahashi M, Shimizu T, et al. Pulmonary surfactant protein D binds MD-2 through the carbohydrate recognition domain. Biochemistry (2008) 47:12878–85.10.1021/bi8010175
    1. LeVine AM, Whitsett JA, Gwozdz JA, Richardson TR, Fisher JH, Burhans MS, et al. Distinct effects of surfactant protein A or D deficiency during bacterial infection on the lung. J Immunol (2000) 165:3934–40.10.4049/jimmunol.165.7.3934
    1. Ikegami M, Scoville EA, Grant S, Korfhagen T, Brondyk W, Scheule RK, et al. Surfactant protein-D and surfactant inhibit endotoxin-induced pulmonary inflammation. Chest (2007) 132:1447–54.10.1378/chest.07-0864
    1. Ikegami M, Carter K, Bishop K, Yadav A, Masterjohn E, Brondyk W, et al. Intratracheal recombinant surfactant protein D prevents endotoxin shock in the newborn preterm lamb. Am J Respir Crit Care Med (2006) 173(12):1342–7.10.1164/rccm.200509-1485OC
    1. Gardai SJ, Xiao YQ, Dickinson M, Nick JA, Voelker DR, Greene KE, et al. By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation. Cell (2003) 115:13–23.10.1016/S0092-8674(03)00758-X
    1. Fournier B, Andargachew R, Robin AZ, Laur O, Voelker DR, Lee WY, et al. Surfactant protein D (Sp-D) binds to membrane-proximal domain (D3) of signal regulatory protein alpha (SIRPalpha), a site distant from binding domain of CD47, while also binding to analogous region on signal regulatory protein beta (SIRPbeta). J Biol Chem (2012) 287:19386–98.10.1074/jbc.M111.324533
    1. McCubbrey AL, Sonstein J, Ames TM, Freeman CM, Curtis JL. Glucocorticoids relieve collectin-driven suppression of apoptotic cell uptake in murine alveolar macrophages through downregulation of SIRPalpha. J Immunol (2012) 189:112–9.10.4049/jimmunol.1200984
    1. Guo CJ, Atochina-Vasserman EN, Abramova E, Foley JP, Zaman A, Crouch E, et al. S-nitrosylation of surfactant protein-D controls inflammatory function. PLoS Biol (2008) 6:e266.10.1371/journal.pbio.0060266
    1. Olde Nordkamp MJ, van Eijk M, Urbanus RT, Bont L, Haagsman HP, Meyaard L. Leukocyte-associated Ig-like receptor-1 is a novel inhibitory receptor for surfactant protein D. J Leukoc Biol (2014) 96:105–11.10.1189/jlb.3AB0213-092RR
    1. Yoshida M, Whitsett JA. Alveolar macrophages and emphysema in surfactant protein-D-deficient mice. Respirology (2006) 11(Suppl):S37–40.10.1111/j.1440-1843.2006.00806.x
    1. Nemeth K, Schoppet M, Al-Fakhri N, Helas S, Jessberger R, Hofbauer LC, et al. The role of osteoclast-associated receptor in osteoimmunology. J Immunol (2011) 186:13–8.10.4049/jimmunol.1002483
    1. Fukuzawa T, Ishida J, Kato A, Ichinose T, Ariestanti DM, Takahashi T, et al. Lung surfactant levels are regulated by Ig-Hepta/GPR116 by monitoring surfactant protein D. PLoS One (2013) 8:e69451.10.1371/journal.pone.0069451
    1. Umeda Y, Hasegawa Y, Otsuka M, Ariki S, Takamiya R, Saito A, et al. Surfactant protein D inhibits activation of non-small cell lung cancer-associated mutant EGFR and affects clinical outcomes of patients. Oncogene (2017) 36(46):6432–45.10.1038/onc.2017.253
    1. Jäkel A, Sim RB. The human lung surfactant proteins A (SP-A) and D (SP-D) share similar binding mechanisms and common lignads on macrophages and dendritic cells. J Unsolved Quest (2012) 2:12–8.
    1. Dodagatta-Marri E, Mitchell DA, Pandit H, Sonawani A, Murugaiah V, Idicula-Thomas S, et al. Protein-protein interaction between surfactant protein D and DC-SIGN via C-type lectin domain can suppress HIV-1 transfer. Front Immunol (2017) 8:834.10.3389/fimmu.2017.00834
    1. Nadesalingam J, Bernal AL, Dodds AW, Willis AC, Mahoney DJ, Day AJ, et al. Identification and characterization of a novel interaction between pulmonary surfactant protein D and decorin. J Biol Chem (2003) 278:25678–87.10.1074/jbc.M210186200
    1. Craig-Barnes HA, Doumouras BS, Palaniyar N. Surfactant protein D interacts with alpha2-macroglobulin and increases its innate immune potential. J Biol Chem (2010) 285:13461–70.10.1074/jbc.M110.108837
    1. Holmskov U, Mollenhauer J, Madsen J, Vitved L, Gronlund J, Tornoe I, et al. Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D. Proc Natl Acad Sci U S A (1999) 96:10794–9.10.1073/pnas.96.19.10794
    1. White MR, Crouch E, van Eijk M, Hartshorn M, Pemberton L, Tornoe I, et al. Cooperative anti-influenza activities of respiratory innate immune proteins and neuraminidase inhibitor. Am J Physiol Lung Cell Mol Physiol (2005) 288:L831–40.10.1152/ajplung.00365.2004
    1. Hartshorn KL, White MR, Tecle T, Holmskov U, Crouch EC. Innate defense against influenza A virus: activity of human neutrophil defensins and interactions of defensins with surfactant protein D. J Immunol (2006) 176:6962–72.10.4049/jimmunol.176.11.6962
    1. Doss M, White MR, Tecle T, Gantz D, Crouch EC, Jung G, et al. Interactions of alpha-, beta-, and theta-defensins with influenza A virus and surfactant protein D. J Immunol (2009) 182:7878–87.10.4049/jimmunol.0804049
    1. Nadesalingam J, Reid KB, Palaniyar N. Collectin surfactant protein D binds antibodies and interlinks innate and adaptive immune systems. FEBS Lett (2005) 579:4449–53.10.1016/j.febslet.2005.07.012
    1. Crouch E, Persson A, Chang D, Heuser J. Molecular structure of pulmonary surfactant protein D (SP-D). J Biol Chem (1994) 269:17311–9.
    1. Zhang L, Ikegami M, Crouch EC, Korfhagen TR, Whitsett JA. Activity of pulmonary surfactant protein-D (SP-D) in vivo is dependent on oligomeric structure. J Biol Chem (2001) 276:19214–9.10.1074/jbc.M010191200
    1. Hansen S, Holmskov U. Structural aspects of collectins and receptors for collectins. Immunobiology (1998) 199:165–89.10.1016/S0171-2985(98)80025-9
    1. Perino J, Thielens NM, Crouch E, Spehner D, Crance JM, Favier AL. Protective effect of surfactant protein d in pulmonary vaccinia virus infection: implication of A27 viral protein. Viruses (2013) 5:928–53.10.3390/v5030928
    1. Crouch EC. Surfactant protein-D and pulmonary host defense. Respir Res (2000) 1:93–108.10.1186/rr19
    1. Botas C, Poulain F, Akiyama J, Brown C, Allen L, Goerke J, et al. Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D. Proc Natl Acad Sci U S A (1998) 95:11869–74.10.1073/pnas.95.20.11869
    1. Wert SE, Yoshida M, LeVine AM, Ikegami M, Jones T, Ross GF, et al. Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice. Proc Natl Acad Sci U S A (2000) 97:5972–7.10.1073/pnas.100448997
    1. Atochina EN, Beers MF, Hawgood S, Poulain F, Davis C, Fusaro TT, et al. Surfactant protein-D, A mediator of innate lung immunity, alters the products of NO metabolism. Am J Respir Cell Mol Biol (2004) 30(3):271–9.
    1. Knudsen L, Ochs K, Boxler L, Tornoe I, Lykke-Sorensen G, Mackay RM, et al. Surfactant protein D (SP-D) deficiency is attenuated in humanised mice expressing the Met(11)Thr short nucleotide polymorphism of SP-D: implications for surfactant metabolism in the lung. J Anat (2013) 223:581–92.10.1111/joa.12120
    1. Winkler C, Bahlmann O, Viereck J, Knudsen L, Wedekind D, Hoymann HG, et al. Impact of a Met(11)Thr single nucleotide polymorphism of surfactant protein D on allergic airway inflammation in a murine asthma model. Exp Lung Res (2014) 40:154–63.10.3109/01902148.2014.891062
    1. Ogasawara Y, Voelker DR. The role of the amino-terminal domain and the collagenous region in the structure and the function of rat surfactant protein D. J Biol Chem (1995) 270:19052–8.10.1074/jbc.270.32.19052
    1. Brown-Augsburger P, Hartshorn K, Chang D, Rust K, Fliszar C, Welgus HG, et al. Site-directed mutagenesis of Cys-15 and Cys-20 of pulmonary surfactant protein D. Expression of a trimeric protein with altered anti-viral properties. J Biol Chem (1996) 271:13724–30.10.1074/jbc.271.23.13724
    1. Kingma PS, Zhang L, Ikegami M, Hartshorn K, McCormack FX, Whitsett JA. Correction of pulmonary abnormalities in Sftpd-/- mice requires the collagenous domain of surfactant protein D. J Biol Chem (2006) 281(34):24496–505.10.1074/jbc.M600651200
    1. Clark H, Palaniyar N, Strong P, Edmondson J, Hawgood S, Reid KB. Surfactant protein D reduces alveolar macrophage apoptosis in vivo. J Immunol (2002) 169:2892–9.10.4049/jimmunol.169.6.2892
    1. Knudsen L, Ochs M, Mackay R, Townsend P, Deb R, Muhlfeld C, et al. Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient mice. Respir Res (2007) 8:70.10.1186/1465-9921-8-70
    1. Strong P, Reid KB, Clark H. Intranasal delivery of a truncated recombinant human SP-D is effective at down-regulating allergic hypersensitivity in mice sensitized to allergens of Aspergillus fumigatus. Clin Exp Immunol (2002) 130:19–24.10.1046/j.1365-2249.2002.01968.x
    1. Strong P, Townsend P, Mackay R, Reid KB, Clark HW. A recombinant fragment of human SP-D reduces allergic responses in mice sensitized to house dust mite allergens. Clin Exp Immunol (2003) 134:181–7.10.1046/j.1365-2249.2003.02281.x
    1. Singh M, Madan T, Waters P, Sonar S, Singh SK, Kamran MF, et al. Therapeutic effects of recombinant forms of full-length and truncated human surfactant protein D in a murine model of invasive pulmonary aspergillosis. Mol Immunol (2009) 46:2363–9.10.1016/j.molimm.2009.03.019
    1. Erpenbeck VJ, Ziegert M, Cavalet-Blanco D, Martin C, Baelder R, Glaab T, et al. Surfactant protein D inhibits early airway response in Aspergillus fumigatus-sensitized mice. Clin Exp Allergy (2006) 36:930–40.10.1111/j.1365-2222.2006.02524.x
    1. Heidinger K, Konig IR, Bohnert A, Kleinsteiber A, Hilgendorff A, Gortner L, et al. Polymorphisms in the human surfactant protein-D (SFTPD) gene: strong evidence that serum levels of surfactant protein-D (SP-D) are genetically influenced. Immunogenetics (2005) 57:1–7.10.1007/s00251-005-0775-5
    1. Sorensen GL, Hjelmborg JB, Kyvik KO, Fenger M, Hoj A, Bendixen C, et al. Genetic and environmental influences of surfactant protein D serum levels. Am J Physiol Lung Cell Mol Physiol (2006) 290:L1010–7.10.1152/ajplung.00487.2005
    1. Lahti M, Lofgren J, Marttila R, Renko M, Klaavuniemi T, Haataja R, et al. Surfactant protein D gene polymorphism associated with severe respiratory syncytial virus infection. Pediatr Res (2002) 51:696–9.10.1203/00006450-200206000-00006
    1. Liu W, Bentley CM, Floros J. Study of human SP-A, SP-B and SP-D loci: allele frequencies, linkage disequilibrium and heterozygosity in different races and ethnic groups. BMC Genet (2003) 4:13.10.1186/1471-2156-4-13
    1. Horimasu Y, Hattori N, Ishikawa N, Tanaka S, Bonella F, Ohshimo S, et al. Differences in serum SP-D levels between German and Japanese subjects are associated with SFTPD gene polymorphisms. BMC Med Genet (2014) 15:4.10.1186/1471-2350-15-4
    1. Johansson SL, Tan Q, Holst R, Christiansen L, Hansen NC, Hojland AT, et al. Surfactant protein D is a candidate biomarker for subclinical tobacco smoke-induced lung damage. Am J Physiol Lung Cell Mol Physiol (2014) 306:L887–95.10.1152/ajplung.00340.2013
    1. Kristiansen M, Frisch M, Madsen HO, Garred P, Jacobsen S. Smoking and polymorphisms of genes encoding mannose-binding lectin and surfactant protein-D in patients with rheumatoid arthritis. Rheumatol Int (2014) 34:373–80.10.1007/s00296-013-2904-z
    1. Sorensen GL, Bladbjerg EM, Steffensen R, Tan Q, Madsen J, Drivsholm T, et al. Association between the surfactant protein D (SFTPD) gene and subclinical carotid artery atherosclerosis. Atherosclerosis (2016) 246:7–12.10.1016/j.atherosclerosis.2015.12.037
    1. Shakoori TA, Sin DD, Bokhari SN, Ghafoor F, Shakoori AR. SP-D polymorphisms and the risk of COPD. Dis Markers (2012) 33:91–100.10.3233/DMA-2012-0909
    1. Kim DK, Cho MH, Hersh CP, Lomas DA, Miller BE, Kong X, et al. Genome-wide association analysis of blood biomarkers in chronic obstructive pulmonary disease. Am J Respir Crit Care Med (2012) 186:1238–47.10.1164/rccm.201206-1013OC
    1. Fakih D, Akiki Z, Junker K, Medlej-Hashim M, Waked M, Salameh P, et al. Surfactant protein D (SP-D) levels, polymorphisms and multimerization in COPD and asthma. Respirology (2017).10.1111/resp.13193
    1. Lin Z, Pearson C, Chinchilli V, Pietschmann SM, Luo J, Pison U, et al. Polymorphisms of human SP-A, SP-B, and SP-D genes: association of SP-B Thr131Ile with ARDS. Clin Genet (2000) 58:181–91.10.1034/j.1399-0004.2000.580305.x
    1. Deng YQ, Tao ZZ, Kong YG, Xiao BK, Chen SM, Xu Y, et al. Association between single nucleotide polymorphisms of surfactant protein D and allergic rhinitis in Chinese patients. Tissue Antigens (2009) 73:546–52.10.1111/j.1399-0039.2009.01232.x
    1. Krueger M, Puthothu B, Gropp E, Heinze J, Braun S, Heinzmann A. Amino acid variants in surfactant protein D are not associated with bronchial asthma. Pediatr Allergy Immunol (2006) 17:77–81.10.1111/j.1399-3038.2005.00353.x
    1. Brandt EB, Mingler MK, Stevenson MD, Wang N, Khurana Hershey GK, Whitsett JA, et al. Surfactant protein D alters allergic lung responses in mice and human subjects. J Allergy Clin Immunol (2008) 121:1140–7.e1142.10.1016/j.jaci.2008.02.011
    1. Berg KK, Madsen HO, Garred P, Wiseth R, Gunnes S, Videm V. The additive contribution from inflammatory genetic markers on the severity of cardiovascular disease. Scand J Immunol (2009) 69:36–42.10.1111/j.1365-3083.2008.02187.x
    1. Aramini B, Kim C, Diangelo S, Petersen E, Lederer DJ, Shah L, et al. Donor surfactant protein D (SP-D) polymorphisms are associated with lung transplant outcome. Am J Transplant (2013) 13:2130–6.10.1111/ajt.12326
    1. Foreman MG, Kong X, Demeo DL, Pillai SG, Hersh CP, Bakke P, et al. Polymorphisms in surfactant protein D are associated with COPD. Am J Respir Cell Mol Biol (2010) 44(3):316–22.10.1165/rcmb.2009-0360OC
    1. Ishii T, Hagiwara K, Kamio K, Ikeda S, Arai T, Mieno MN, et al. Involvement of surfactant protein D in emphysema revealed by genetic association study. Eur J Hum Genet (2012) 20:230–5.10.1038/ejhg.2011.183
    1. Ou CY, Chen CZ, Hsiue TR, Lin SH, Wang JY. Genetic variants of pulmonary SP-D predict disease outcome of COPD in a Chinese population. Respirology (2015) 20:296–303.10.1111/resp.12427
    1. Garcia-Laorden MI, Rodriguez de Castro F, Sole-Violan J, Rajas O, Blanquer J, Borderias L, et al. Influence of genetic variability at the surfactant proteins A and D in community-acquired pneumonia: a prospective, observational, genetic study. Crit Care (2011) 15:R57.10.1186/cc10030
    1. Soto-Cardenas MJ, Gandia M, Brito-Zeron P, Arias MT, Armiger N, Bove A, et al. Etiopathogenic role of surfactant protein d in the clinical and immunological expression of primary Sjogren syndrome. J Rheumatol (2015) 42:111–8.10.3899/jrheum.140394
    1. Pueyo N, Ortega FJ, Mercader JM, Moreno-Navarrete JM, Sabater M, Bonas S, et al. Common genetic variants of surfactant protein-D (SP-D) are associated with type 2 diabetes. PLoS One (2013) 8:e60468.10.1371/journal.pone.0060468
    1. Lin Z, John G, Hegarty JP, Berg A, Yu W, Wang Y, et al. Genetic variants and monoallelic expression of surfactant protein-D in inflammatory bowel disease. Ann Hum Genet (2011) 75:559–68.10.1111/j.1469-1809.2011.00662.x
    1. Ishii T, Hagiwara K, Ikeda S, Arai T, Mieno MN, Kumasaka T, et al. Association between genetic variations in surfactant protein d and emphysema, interstitial pneumonia, and lung cancer in a Japanese population. COPD (2012) 9:409–16.10.3109/15412555.2012.676110
    1. Pavlovic J, Papagaroufalis C, Xanthou M, Liu W, Fan R, Thomas NJ, et al. Genetic variants of surfactant proteins A, B, C, and D in bronchopulmonary dysplasia. Dis Markers (2006) 22:277–91.10.1155/2006/817805
    1. Sorensen GL, Dahl M, Tan Q, Bendixen C, Holmskov U, Husby S. Surfactant protein-D-encoding gene variant polymorphisms are linked to respiratory outcome in premature infants. J Pediatr (2014) 165:683–9.10.1016/j.jpeds.2014.05.042
    1. Hilgendorff A, Heidinger K, Bohnert A, Kleinsteiber A, Konig IR, Ziegler A, et al. Association of polymorphisms in the human surfactant protein-D (SFTPD) gene and postnatal pulmonary adaptation in the preterm infant. Acta Paediatr (2009) 98:112–7.10.1111/j.1651-2227.2008.01014.x
    1. Karjalainen MK, Huusko JM, Tuohimaa A, Luukkonen A, Haataja R, Hallman M. A study of collectin genes in spontaneous preterm birth reveals an association with a common surfactant protein D gene polymorphism. Pediatr Res (2012) 71:93–9.10.1038/pr.2011.2
    1. Thomas NJ, DiAngelo S, Hess JC, Fan R, Ball MW, Geskey JM, et al. Transmission of surfactant protein variants and haplotypes in children hospitalized with respiratory syncytial virus. Pediatr Res (2009) 66:70–3.10.1203/PDR.0b013e3181a1d768
    1. Floros J, Lin HM, Garcia A, Salazar MA, Guo X, DiAngelo S, et al. Surfactant protein genetic marker alleles identify a subgroup of tuberculosis in a Mexican population. J Infect Dis (2000) 182:1473–8.10.1086/315866
    1. Persson A, Chang D, Rust K, Moxley M, Longmore W, Crouch E. Purification and biochemical characterization of CP4 (SP-D), a collagenous surfactant-associated protein. Biochemistry (1989) 28:6361–7.10.1021/bi00441a031
    1. Crouch E, Chang D, Rust K, Persson A, Heuser J. Recombinant pulmonary surfactant protein D. Post-translational modification and molecular assembly. J Biol Chem (1994) 269:15808–13.
    1. Leth-Larsen R, Holmskov U, Hojrup P. Structural characterization of human and bovine lung surfactant protein D. Biochem J (1999) 343(Pt 3):645–52.10.1042/0264-6021:3430645
    1. Ito E, Oka R, Ishii T, Korekane H, Kurimoto A, Kizuka Y, et al. Fucosylated surfactant protein-D is a biomarker candidate for the development of chronic obstructive pulmonary disease. J Proteomics (2015) 127:386–94.10.1016/j.jprot.2015.07.011
    1. Atochina-Vasserman EN, Winkler C, Abramova H, Schaumann F, Krug N, Gow AJ, et al. Segmental allergen challenge alters multimeric structure and function of surfactant protein d in humans. Am J Respir Crit Care Med (2011) 183:856–64.10.1164/rccm.201004-0654OC
    1. Atochina-Vasserman EN, Guo CJ, Abramova E, Golden TN, Sims M, James ML, et al. Surfactant dysfunction and lung inflammation in the female mouse model of lymphangioleiomyomatosis. Am J Respir Cell Mol Biol (2015) 53:96–104.10.1165/rcmb.2014-0224OC
    1. Guo C, Atochina-Vasserman E, Abramova H, George B, Manoj V, Scott P, et al. Role of NOS2 in pulmonary injury and repair in response to bleomycin. Free Radic Biol Med (2016) 91:293–301.10.1016/j.freeradbiomed.2015.10.417
    1. Atochina-Vasserman EN, Gow AJ, Abramova H, Guo CJ, Tomer Y, Preston AM, et al. Immune reconstitution during Pneumocystis lung infection: disruption of surfactant component expression and function by S-nitrosylation. J Immunol (2009) 182:2277–87.10.4049/jimmunol.0802775
    1. Malaviya R, Gow AJ, Francis M, Abramova EV, Laskin JD, Laskin DL. Radiation-induced lung injury and inflammation in mice: role of inducible nitric oxide synthase and surfactant protein D. Toxicol Sci (2015) 144:27–38.10.1093/toxsci/kfu255
    1. Matalon S, Shrestha K, Kirk M, Waldheuser S, McDonald B, Smith K, et al. Modification of surfactant protein D by reactive oxygen-nitrogen intermediates is accompanied by loss of aggregating activity, in vitro and in vivo. FASEB J (2009) 23:1415–30.10.1096/fj.08-120568
    1. Crouch EC, Hirche TO, Shao B, Boxio R, Wartelle J, Benabid R, et al. Myeloperoxidase-dependent inactivation of surfactant protein D in vitro and in vivo. J Biol Chem (2010) 285:16757–70.10.1074/jbc.M109.097048
    1. Cooley J, McDonald B, Accurso FJ, Crouch EC, Remold-O’Donnell E. Patterns of neutrophil serine protease-dependent cleavage of surfactant protein D in inflammatory lung disease. J Leukoc Biol (2008) 83:946–55.10.1189/jlb.1007684
    1. Duvoix A, Mackay RM, Henderson N, McGreal E, Postle A, Reid K, et al. Physiological concentration of calcium inhibits elastase-induced cleavage of a functional recombinant fragment of surfactant protein D. Immunobiology (2011) 216:72–9.10.1016/j.imbio.2010.03.006
    1. Alcorn JF, Wright JR. Degradation of pulmonary surfactant protein D by Pseudomonas aeruginosa elastase abrogates innate immune function. J Biol Chem (2004) 279:30871–9.10.1074/jbc.M400796200
    1. Winkler C, Atochina-Vasserman EN, Holz O, Beers MF, Erpenbeck VJ, Krug N, et al. Comprehensive characterisation of pulmonary and serum surfactant protein D in COPD. Respir Res (2011) 12:29.10.1186/1465-9921-12-29
    1. Mariencheck WI, Alcorn JF, Palmer SM, Wright JR. Pseudomonas aeruginosa elastase degrades surfactant proteins A and D. Am J Respir Cell Mol Biol (2003) 28:528–37.10.1165/rcmb.2002-0141OC
    1. von Bredow C, Wiesener A, Griese M. Proteolysis of surfactant protein D by cystic fibrosis relevant proteases. Lung (2003) 181:79–88.10.1007/s00408-003-1008-z
    1. Hirche TO, Crouch EC, Espinola M, Brokelman TJ, Mecham RP, DeSilva N, et al. Neutrophil serine proteinases inactivate surfactant protein D by cleaving within a conserved subregion of the carbohydrate recognition domain. J Biol Chem (2004) 279:27688–98.10.1074/jbc.M402936200
    1. Malloy JL, Veldhuizen RA, Thibodeaux BA, O’Callaghan RJ, Wright JR. Pseudomonas aeruginosa protease IV degrades surfactant proteins and inhibits surfactant host defense and biophysical functions. Am J Physiol Lung Cell Mol Physiol (2005) 288:L409–18.10.1152/ajplung.00322.2004
    1. Deb R, Shakib F, Reid K, Clark H. Major house dust mite allergens Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1 degrade and inactivate lung surfactant proteins A and D. J Biol Chem (2007) 282:36808–19.10.1074/jbc.M702336200
    1. Mun JJ, Tam C, Kowbel D, Hawgood S, Barnett MJ, Evans DJ, et al. Clearance of Pseudomonas aeruginosa from a healthy ocular surface involves surfactant protein D and is compromised by bacterial elastase in a murine null-infection model. Infect Immun (2009) 77:2392–8.10.1128/IAI.00173-09
    1. Bratcher PE, Weathington NM, Nick HJ, Jackson PL, Snelgrove RJ, Gaggar A. MMP-9 cleaves SP-D and abrogates its innate immune functions in vitro. PLoS One (2012) 7:e41881.10.1371/journal.pone.0041881
    1. Stolley JM, Gong D, Farley K, Zhao P, Cooley J, Crouch EC, et al. Increased surfactant protein D fails to improve bacterial clearance and inflammation in serpinB1-/- mice. Am J Respir Cell Mol Biol (2012) 47:792–9.10.1165/rcmb.2012-0145OC
    1. Zhang Z, Abdel-Razek O, Hawgood S, Wang G. Protective role of surfactant protein D in ocular Staphylococcus aureus infection. PLoS One (2015) 10:e0138597.10.1371/journal.pone.0138597
    1. Todd DA, Marsh MJ, George A, Henderson NG, Barr H, Sebastian S, et al. Surfactant phospholipids, surfactant proteins, and inflammatory markers during acute lung injury in children. Pediatr Crit Care Med (2010) 11:82–91.10.1097/PCC.0b013e3181ae5a4c
    1. Griese M, Wiesener A, Lottspeich F, von Bredow C. Limited proteolysis of surfactant protein D causes a loss of its calcium-dependent lectin functions. Biochim Biophys Acta (2003) 1638:157–63.10.1016/S0925-4439(03)00063-2
    1. Noah TL, Murphy PC, Alink JJ, Leigh MW, Hull WM, Stahlman MT, et al. Bronchoalveolar lavage fluid surfactant protein-A and surfactant protein-D are inversely related to inflammation in early cystic fibrosis. Am J Respir Crit Care Med (2003) 168:685–91.10.1164/rccm.200301-005OC
    1. Postle AD, Mander A, Reid KB, Wang JY, Wright SM, Moustaki M, et al. Deficient hydrophilic lung surfactant proteins A and D with normal surfactant phospholipid molecular species in cystic fibrosis. Am J Respir Cell Mol Biol (1999) 20:90–8.10.1165/ajrcmb.20.1.3253
    1. Griese M, Steinecker M, Schumacher S, Braun A, Lohse P, Heinrich S. Children with absent surfactant protein D in bronchoalveolar lavage have more frequently pneumonia. Pediatr Allergy Immunol (2008) 19:639–47.10.1111/j.1399-3038.2007.00695.x
    1. Griese M, Maderlechner N, Ahrens P, Kitz R. Surfactant proteins A and D in children with pulmonary disease due to gastroesophageal reflux. Am J Respir Crit Care Med (2002) 165:1546–50.10.1164/rccm.2107147
    1. Umstead TM, Freeman WM, Chinchilli VM, Phelps DS. Age-related changes in the expression and oxidation of bronchoalveolar lavage proteins in the rat. Am J Physiol Lung Cell Mol Physiol (2009) 296:L14–29.10.1152/ajplung.90366.2008
    1. Betsuyaku T, Kuroki Y, Nagai K, Nasuhara Y, Nishimura M. Effects of ageing and smoking on SP-A and SP-D levels in bronchoalveolar lavage fluid. Eur Respir J (2004) 24:964–70.10.1183/09031936.04.00064004
    1. Moliva JI, Rajaram MV, Sidiki S, Sasindran SJ, Guirado E, Pan XJ, et al. Molecular composition of the alveolar lining fluid in the aging lung. Age (Dordr) (2014) 36:9633.10.1007/s11357-014-9633-4
    1. Zhao XM, Wu YP, Wei R, Cai HX, Tornoe I, Han JJ, et al. Plasma surfactant protein D levels and the relation to body mass index in a chinese population. Scand J Immunol (2007) 66:71–6.10.1111/j.1365-3083.2007.01943.x
    1. Ilumets H, Mazur W, Toljamo T, Louhelainen N, Nieminen P, Kobayashi H, et al. Ageing and smoking contribute to plasma surfactant proteins and protease imbalance with correlations to airway obstruction. BMC Pulm Med (2011) 11:19.10.1186/1471-2466-11-19
    1. Benfante A, Battaglia S, Principe S, Di Mitri C, Paterno A, Spatafora M, et al. Asthmatics with high levels of serum surfactant protein D have more severe disease. Eur Respir J (2016) 47(6):1864–7.10.1183/13993003.02142-2015
    1. Hastings RH, Grady M, Sakuma T, Matthay MA. Clearance of different-sized proteins from the alveolar space in humans and rabbits. J Appl Physiol (1985) (1992) 73:1310–6.10.1152/jappl.1992.73.4.1310
    1. Gaunsbaek MQ, Rasmussen KJ, Beers MF, Atochina-Vasserman EN, Hansen S. Lung surfactant protein D (SP-D) response and regulation during acute and chronic lung injury. Lung (2013) 191:295–303.10.1007/s00408-013-9452-x
    1. Hirama N, Shibata Y, Otake K, Machiya J, Wada T, Inoue S, et al. Increased surfactant protein-D and foamy macrophages in smoking-induced mouse emphysema. Respirology (2007) 12:191–201.10.1111/j.1440-1843.2006.01009.x
    1. Moazed F, Burnham EL, Vandivier RW, O’Kane CM, Shyamsundar M, Hamid U, et al. Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation. Thorax (2016) 71(12):1130–6.10.1136/thoraxjnl-2015-207886
    1. More JM, Voelker DR, Silveira LJ, Edwards MG, Chan ED, Bowler RP. Smoking reduces surfactant protein D and phospholipids in patients with and without chronic obstructive pulmonary disease. BMC Pulm Med (2010) 10:53.10.1186/1471-2466-10-53
    1. Sims MW, Tal-Singer RM, Kierstein S, Musani AI, Beers MF, Panettieri RA, et al. Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study. Respir Res (2008) 9:13.10.1186/1465-9921-9-13
    1. Lomas DA, Silverman EK, Edwards LD, Locantore NW, Miller BE, Horstman DH, et al. Serum surfactant protein D is steroid sensitive and associated with exacerbations of COPD. Eur Respir J (2009) 34(1):95–102.10.1183/09031936.00156508
    1. Krane M, Griese M. Surfactant protein D in serum from patients with allergic bronchopulmonary aspergillosis. Eur Respir J (2003) 22:592–5.10.1183/09031936.03.00060603
    1. Olesen HV, Holmskov U, Schiotz PO, Sorensen GL. Serum-surfactant SP-D correlates inversely to lung function in cystic fibrosis. J Cyst Fibros (2010) 9:257–62.10.1016/j.jcf.2010.03.011
    1. Herbein JF, Wright JR. Enhanced clearance of surfactant protein D during LPS-induced acute inflammation in rat lung. Am J Physiol Lung Cell Mol Physiol (2001) 281:L268–77.10.1152/ajplung.2001.281.1.L268
    1. Atochina-Vasserman EN. S-nitrosylation of surfactant protein D as a modulator of pulmonary inflammation. Biochim Biophys Acta (2012) 1820:763–9.10.1016/j.bbagen.2011.12.006
    1. Starosta V, Griese M. Oxidative damage to surfactant protein D in pulmonary diseases. Free Radic Res (2006) 40:419–25.10.1080/10715760600571248
    1. Duvoix A, Miranda E, Perez J, Sorensen GL, Holmskov U, Trapnell BC, et al. Evaluation of full-length, cleaved and nitrosylated serum surfactant protein D as biomarkers for COPD. COPD (2011) 8:79–95.10.3109/15412555.2011.558542
    1. Celli BR, Locantore N, Yates J, Tal-Singer R, Miller BE, Bakke P, et al. Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. Am J Respir Crit Care Med (2012) 185:1065–72.10.1164/rccm.201110-1792OC
    1. Barlo NP, van Moorsel CH, Ruven HJ, Zanen P, van den Bosch JM, Grutters JC. Surfactant protein-D predicts survival in patients with idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis (2009) 26:155–61.
    1. Eisner MD, Parsons P, Matthay MA, Ware L, Greene K, Acute Respiratory Distress Syndrome Network . Plasma surfactant protein levels and clinical outcomes in patients with acute lung injury. Thorax (2003) 58:983–8.10.1136/thorax.58.11.983
    1. Cheng IW, Ware LB, Greene KE, Nuckton TJ, Eisner MD, Matthay MA. Prognostic value of surfactant proteins A and D in patients with acute lung injury. Crit Care Med (2003) 31:20–7.10.1097/00003246-200301000-00003
    1. Ware LB, Koyama T, Billheimer DD, Wu W, Bernard GR, Thompson BT, et al. Prognostic and pathogenetic value of combining clinical and biochemical indices in patients with acute lung injury. Chest (2010) 137:288–96.10.1378/chest.09-1484
    1. Ware LB, Koyama T, Zhao Z, Janz DR, Wickersham N, Bernard GR, et al. Biomarkers of lung epithelial injury and inflammation distinguish severe sepsis patients with acute respiratory distress syndrome. Crit Care (2013) 17:R253.10.1186/cc13080
    1. King BA, Kingma PS. Surfactant protein D deficiency increases lung injury during endotoxemia. Am J Respir Cell Mol Biol (2011) 44:709–15.10.1165/rcmb.2009-0436OC
    1. Determann RM, Royakkers AA, Haitsma JJ, Zhang H, Slutsky AS, Ranieri VM, et al. Plasma levels of surfactant protein D and KL-6 for evaluation of lung injury in critically ill mechanically ventilated patients. BMC Pulm Med (2010) 10:6.10.1186/1471-2466-10-6
    1. Ryckman KK, Dagle JM, Kelsey K, Momany AM, Murray JC. Genetic associations of surfactant protein D and angiotensin-converting enzyme with lung disease in preterm neonates. J Perinatol (2012) 32:349–55.10.1038/jp.2011.104
    1. Leth-Larsen R, Nordenbaek C, Tornoe I, Moeller V, Schlosser A, Koch C, et al. Surfactant protein D (SP-D) serum levels in patients with community-acquired pneumonia. Clin Immunol (2003) 108:29–37.10.1016/S1521-6616(03)00042-1
    1. Jambo KC, French N, Zijlstra E, Gordon SB. AIDS patients have increased surfactant protein D but normal mannose binding lectin levels in lung fluid. Respir Res (2007) 8:42.10.1186/1465-9921-8-42
    1. Wu YP, Liu ZH, Wei R, Pan SD, Mao NY, Chen B, et al. Elevated plasma surfactant protein D (SP-D) levels and a direct correlation with anti-severe acute respiratory syndrome coronavirus-specific IgG antibody in SARS patients. Scand J Immunol (2009) 69:508–15.10.1111/j.1365-3083.2009.02245.x
    1. Hartshorn KL, White MR, Tecle T, Sorensen G, Holmskov U, Crouch EC. Viral aggregating and opsonizing activity in collectin trimers. Am J Physiol Lung Cell Mol Physiol (2010) 298:L79–88.10.1152/ajplung.00223.2009
    1. Boonarkart CH, Suptawiwat O, Uiprasertkul M, Kongchanagul A, Rodpothong P, Bunthi CH, et al. A reduced expression of surfactant protein D in the lungs of fatal influenza H1N1 cases in 2009. Acta Virol (2012) 56:253–5.10.4149/av_2012_03_253
    1. Sin DD, Man SF, McWilliams A, Lam S. Surfactant protein D and bronchial dysplasia in smokers at high risk of lung cancer. Chest (2008) 134:582–8.10.1378/chest.08-0600
    1. Shiels MS, Chaturvedi AK, Katki HA, Gochuico BR, Caporaso NE, Engels EA. Circulating markers of interstitial lung disease and subsequent risk of lung cancer. Cancer Epidemiol Biomarkers Prev (2011) 20:2262–72.10.1158/1055-9965.EPI-11-0326
    1. Ichiyasu H, Ichikado K, Yamashita A, Iyonaga K, Sakamoto O, Suga M, et al. Pneumocyte biomarkers KL-6 and surfactant protein D reflect the distinct findings of high-resolution computed tomography in nonspecific interstitial pneumonia. Respiration (2012) 83:190–7.10.1159/000326924
    1. White ES, Xia M, Murray S, Dyal R, Flaherty CM, Flaherty KR, et al. Plasma surfactant protein-D, matrix metalloproteinase-7, and osteopontin index distinguishes idiopathic pulmonary fibrosis from other idiopathic interstitial pneumonias. Am J Respir Crit Care Med (2016) 194(10):1242–51.10.1164/rccm.201505-0862OC
    1. Nakamura K, Kato M, Shukuya T, Mori K, Sekimoto Y, Ihara H, et al. Surfactant protein-D predicts prognosis of interstitial lung disease induced by anticancer agents in advanced lung cancer: a case control study. BMC Cancer (2017) 17:302.10.1186/s12885-017-3285-6
    1. Thomas NJ, Fan R, Diangelo S, Hess JC, Floros J. Haplotypes of the surfactant protein genes A and D as susceptibility factors for the development of respiratory distress syndrome. Acta Paediatr (2007) 96:985–9.10.1111/j.1651-2227.2007.00319.x
    1. Chang HY, Li F, Li FS, Zheng CZ, Lei YZ, Wang J. Genetic polymorphisms of SP-A, SP-B, and SP-D and risk of respiratory distress syndrome in preterm neonates. Med Sci Monit (2016) 22:5091–100.10.12659/MSM.898553
    1. Gower WA, Nogee LM. Candidate gene analysis of the surfactant protein D gene in pediatric diffuse lung disease. J Pediatr (2013) 163:1778–80.10.1016/j.jpeds.2013.06.063
    1. Kotecha S, Davies PL, Clark HW, McGreal EP. Increased prevalence of low oligomeric state surfactant protein D with restricted lectin activity in bronchoalveolar lavage fluid from preterm infants. Thorax (2013) 68:460–7.10.1136/thoraxjnl-2012-202729
    1. Nakamura T, Shimizu H, Nishitani C, Yoshioka T. Remarkably delayed occurrence of normal surfactant composition in an extremely preterm infant. Pediatr Int (2013) 55:790–2.10.1111/ped.12202
    1. Bae YM, Bae CW, Oh MH, Lee SH, Woo KM, Jung KB. Effect of exogenous surfactant therapy on levels of pulmonary surfactant proteins A and D in preterm infants with respiratory distress syndrome. J Perinat Med (2009) 37:561–4.10.1515/JPM.2009.100
    1. Beresford MW, Shaw NJ. Bronchoalveolar lavage surfactant protein a, B, and d concentrations in preterm infants ventilated for respiratory distress syndrome receiving natural and synthetic surfactants. Pediatr Res (2003) 53:663–70.10.1203/01.PDR.0000054653.89527.F8
    1. Dahl M, Holmskov U, Husby S, Juvonen PO. Surfactant protein D levels in umbilical cord blood and capillary blood of premature infants. The influence of peri-natal factors. Pediatr Res (2006) 59(6):806–10.10.1203/01.pdr.0000219122.81734.03
    1. Vinod S, Gow A, Weinberger B, Potak D, Hiatt M, Chandra S, et al. Serum surfactant protein D as a marker for bronchopulmonary dysplasia. J Matern Fetal Neonatal Med (2017) 26:1–5.10.1080/14767058.2017.1392506
    1. Ogasawara Y, Kuroki Y, Shiratori M, Shimizu H, Miyamura K, Akino T. Ontogeny of surfactant apoprotein D, SP-D, in the rat lung. Biochim Biophys Acta (1991) 1083:252–6.10.1016/0005-2760(91)90079-W
    1. Chen CM, Wang LF. High-dose vascular endothelial growth factor increases surfactant protein gene expressions in preterm rat lung. Early Hum Dev (2007) 83:581–4.10.1016/j.earlhumdev.2006.12.005
    1. Lykkedegn S, Sorensen GL, Beck-Nielsen SS, Pilecki B, Duelund L, Marcussen N, et al. Vitamin D depletion in pregnancy decreases survival time, oxygen saturation, lung weight and body weight in preterm rat offspring. PLoS One (2016) 11:e0155203.10.1371/journal.pone.0155203
    1. Bersani I, Speer CP, Kunzmann S. Surfactant proteins A and D in pulmonary diseases of preterm infants. Expert Rev Anti Infect Ther (2012) 10:573–84.10.1586/eri.12.34
    1. Awasthi S, Coalson JJ, Crouch E, Yang F, King RJ. Surfactant proteins A and D in premature baboons with chronic lung injury (bronchopulmonary dysplasia). Evidence for an inhibition of secretion. Am J Respir Crit Care Med (1999) 160:942–9.10.1164/ajrccm.160.3.9806061
    1. Awasthi S, Coalson JJ, Yoder BA, Crouch E, King RJ. Deficiencies in lung surfactant proteins A and D are associated with lung infection in very premature neonatal baboons. Am J Respir Crit Care Med (2001) 163:389–97.10.1164/ajrccm.163.2.2004168
    1. Jain D, Atochina-Vasserman E, Kadire H, Tomer Y, Inch A, Scott P, et al. SP-D-deficient mice are resistant to hyperoxia. Am J Physiol Lung Cell Mol Physiol (2007) 292:L861–71.10.1152/ajplung.00145.2006
    1. Kallapur SG, Moss TJ, Ikegami M, Jasman RL, Newnham JP, Jobe AH. Recruited inflammatory cells mediate endotoxin-induced lung maturation in preterm fetal lambs. Am J Respir Crit Care Med (2005) 172:1315–21.10.1164/rccm.200506-1007OC
    1. Jobe AH, Newnham JP, Willet KE, Sly P, Ervin MG, Bachurski C, et al. Effects of antenatal endotoxin and glucocorticoids on the lungs of preterm lambs. Am J Obstet Gynecol (2000) 182:401–8.10.1016/S0002-9378(00)70231-6
    1. Bry K, Lappalainen U. Intra-amniotic endotoxin accelerates lung maturation in fetal rabbits. Acta Paediatr (2001) 90:74–80.10.1111/j.1651-2227.2001.tb00259.x
    1. Alexander JM, Gilstrap LC, Cox SM, McIntire DM, Leveno KJ. Clinical chorioamnionitis and the prognosis for very low birth weight infants. Obstet Gynecol (1998) 91:725–9.10.1097/00006250-199805000-00016
    1. Andrews WW, Goldenberg RL, Faye-Petersen O, Cliver S, Goepfert AR, Hauth JC. The Alabama Preterm Birth study: polymorphonuclear and mononuclear cell placental infiltrations, other markers of inflammation, and outcomes in 23- to 32-week preterm newborn infants. Am J Obstet Gynecol (2006) 195:803–8.10.1016/j.ajog.2006.06.083
    1. Chaiworapongsa T, Hong JS, Hull WM, Romero R, Whitsett JA. Amniotic fluid concentration of surfactant proteins in intra-amniotic infection. J Matern Fetal Neonatal Med (2008) 21:663–70.10.1080/14767050802215664
    1. Schmiedl A, Behrens J, Zscheppang K, Purevdorj E, von Mayersbach D, Liese A, et al. Lipopolysaccharide-induced injury is more pronounced in fetal transgenic ErbB4-deleted lungs. Am J Physiol Lung Cell Mol Physiol (2011) 301:L490–9.10.1152/ajplung.00131.2010
    1. Kuypers E, Collins JJ, Kramer BW, Ofman G, Nitsos I, Pillow JJ, et al. Intra-amniotic LPS and antenatal betamethasone: inflammation and maturation in preterm lamb lungs. Am J Physiol Lung Cell Mol Physiol (2012) 302:L380–9.10.1152/ajplung.00338.2011
    1. Salminen A, Paananen R, Vuolteenaho R, Metsola J, Ojaniemi M, Autio-Harmainen H, et al. Maternal endotoxin-induced preterm birth in mice: fetal responses in toll-like receptors, collectins, and cytokines. Pediatr Res (2008) 63:280–6.10.1203/PDR.0b013e318163a8b2
    1. Salminen A, Vuolteenaho R, Paananen R, Ojaniemi M, Hallman M. Surfactant protein D modulates levels of IL-10 and TNF-alpha in intrauterine compartments during lipopolysaccharide-induced preterm birth. Cytokine (2012) 60:423–30.10.1016/j.cyto.2012.07.021
    1. Montalbano AP, Hawgood S, Mendelson CR. Mice deficient in surfactant protein A (SP-A) and SP-D or in TLR2 manifest delayed parturition and decreased expression of inflammatory and contractile genes. Endocrinology (2013) 154:483–98.10.1210/en.2012-1797
    1. Kay S, Madan T. Fertility defects in surfactant associated protein D knockout female mice: altered ovarian hormone profile. Mol Immunol (2016) 71:87–97.10.1016/j.molimm.2016.01.002
    1. Sato A, Whitsett JA, Scheule RK, Ikegami M. Surfactant protein-d inhibits lung inflammation caused by ventilation in premature newborn lambs. Am J Respir Crit Care Med (2010) 181:1098–105.10.1164/rccm.200912-1818OC
    1. Xu J, Singhera GK, Dorscheid DR. Expression of surfactant protein D in airways of asthmatics and interleukin-13 modulation of surfactant protein D in human models of airway epithelium. Respir Res (2015) 16:26.10.1186/s12931-015-0177-7
    1. Cheng G, Ueda T, Numao T, Kuroki Y, Nakajima H, Fukushima Y, et al. Increased levels of surfactant protein A and D in bronchoalveolar lavage fluids in patients with bronchial asthma. Eur Respir J (2000) 16:831–5.10.1183/09031936.00.16583100
    1. Koopmans JG, van der Zee JS, Krop EJ, Lopuhaa CE, Jansen HM, Batenburg JJ. Serum surfactant protein D is elevated in allergic patients. Clin Exp Allergy (2004) 34:1827–33.10.1111/j.1365-2222.2004.02083.x
    1. Emmanouil P, Loukides S, Kostikas K, Papatheodorou G, Papaporfyriou A, Hillas G, et al. Sputum and BAL Clara cell secretory protein and surfactant protein D levels in asthma. Allergy (2015) 70:711–4.10.1111/all.12603
    1. Okazaki S, Murai H, Kidoguchi S, Nomura E, Itoh N, Hashimoto N, et al. The biomarker salivary SP-D may indicate small airway inflammation and asthma exacerbation. J Investig Allergol Clin Immunol (2017) 27:305–12.10.18176/jiaci.0174
    1. Mutti A, Corradi M, Goldoni M, Vettori MV, Bernard A, Apostoli P. Exhaled metallic elements and serum pneumoproteins in asymptomatic smokers and patients with COPD or asthma. Chest (2006) 129:1288–97.10.1378/chest.129.5.1288
    1. Akiki Z, Fakih D, Jounblat R, Chamat S, Waked M, Holmskov U, et al. Surfactant protein D, a clinical biomarker for chronic obstructive pulmonary disease with excellent discriminant values. Exp Ther Med (2016) 11:723–30.10.3892/etm.2016.2986
    1. Tanaka H, Sugawara H, Saikai T, Tsunematsu K, Takahashi H, Abe S. Mushroom worker’s lung caused by spores of Hypsizygus marmoreus (Bunashimeji): elevated serum surfactant protein D levels. Chest (2000) 118:1506–9.10.1378/chest.118.5.1506
    1. Saikai T, Tanaka H, Fuji M, Sugawara H, Takeya I, Tsunematsu K, et al. Hypersensitivity pneumonitis induced by the spore of Pleurotus eryngii (Eringi). Intern Med (2002) 41:571–3.10.2169/internalmedicine.41.571
    1. Higashi A, Higashi N, Tsuburai T, Takeuchi Y, Taniguchi M, Mita H, et al. Involvement of eicosanoids and surfactant protein D in extrinsic allergic alveolitis. Eur Respir J (2005) 26:1069–73.10.1183/09031936.05.00106104
    1. Tsushima K, Fujimoto K, Yoshikawa S, Kawakami S, Koizumi T, Kubo K. Hypersensitivity pneumonitis due to Bunashimeji mushrooms in the mushroom industry. Int Arch Allergy Immunol (2005) 137:241–8.10.1159/000086337
    1. Inase N, Ohtani Y, Sumi Y, Umino T, Usui Y, Miyake S, et al. A clinical study of hypersensitivity pneumonitis presumably caused by feather duvets. Ann Allergy Asthma Immunol (2006) 96:98–104.10.1016/S1081-1206(10)61047-2
    1. Lambrecht BN, Hammad H. The immunology of asthma. Nat Immunol (2015) 16:45–56.10.1038/ni.3049
    1. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med (2012) 18:716–25.10.1038/nm.2678
    1. Madan T, Reid KB, Singh M, Sarma PU, Kishore U. Susceptibility of mice genetically deficient in the surfactant protein (SP)-A or SP-D gene to pulmonary hypersensitivity induced by antigens and allergens of Aspergillus fumigatus. J Immunol (2005) 174:6943–54.10.4049/jimmunol.174.11.6943
    1. Madan T, Kishore U, Singh M, Strong P, Clark H, Hussain EM, et al. Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens. J Clin Invest (2001) 107:467–75.10.1172/JCI10124
    1. Schaub B, Westlake RM, He H, Arestides R, Haley KJ, Campo M, et al. Surfactant protein D deficiency influences allergic immune responses. Clin Exp Allergy (2004) 34:1819–26.10.1111/j.1365-2222.2004.02068.x
    1. Liu CF, Chen YL, Shieh CC, Yu CK, Reid KB, Wang JY. Therapeutic effect of surfactant protein D in allergic inflammation of mite-sensitized mice. Clin Exp Allergy (2005) 35:515–21.10.1111/j.1365-2222.2005.02205.x
    1. Haczku A, Cao Y, Vass G, Kierstein S, Nath P, Atochina-Vasserman EN, et al. IL-4 and IL-13 form a negative feedback circuit with surfactant protein-D in the allergic airway response. J Immunol (2006) 176:3557–65.10.4049/jimmunol.176.6.3557
    1. Cao Y, Tao JQ, Bates SR, Beers MF, Haczku A. IL-4 induces production of the lung collectin surfactant protein-D. J Allergy Clin Immunol (2004) 113:439–44.10.1016/j.jaci.2003.11.031
    1. Qaseem AS, Sonar S, Mahajan L, Madan T, Sorensen GL, Shamji MH, et al. Linking surfactant protein SP-D and IL-13: implications in asthma and allergy. Mol Immunol (2013) 54:98–107.10.1016/j.molimm.2012.10.039
    1. Kasper M, Sims G, Koslowski R, Kuss H, Thuemmler M, Fehrenbach H, et al. Increased surfactant protein D in rat airway goblet and Clara cells during ovalbumin-induced allergic airway inflammation. Clin Exp Allergy (2002) 32:1251–8.10.1046/j.1365-2745.2002.01423.x
    1. Fahy JV. Type 2 inflammation in asthma – present in most, absent in many. Nat Rev Immunol (2015) 15:57–65.10.1038/nri3807
    1. Wang JY, Shieh CC, You PF, Lei HY, Reid KB. Inhibitory effect of pulmonary surfactant proteins A and D on allergen-induced lymphocyte proliferation and histamine release in children with asthma. Am J Respir Crit Care Med (1998) 158:510–8.10.1164/ajrccm.158.2.9709111
    1. Atochina EN, Beers MF, Tomer Y, Scanlon ST, Russo SJ, Panettieri RA, Jr, et al. Attenuated allergic airway hyperresponsiveness in C57BL/6 mice is associated with enhanced surfactant protein (SP)-D production following allergic sensitization. Respir Res (2003) 4:15.10.1186/1465-9921-4-15
    1. van Diemen CC, Postma DS, Aulchenko YS, Snijders PJ, Oostra BA, van Duijn CM, et al. Novel strategy to identify genetic risk factors for COPD severity: a genetic isolate. Eur Respir J (2010) 35:768–75.10.1183/09031936.00054408
    1. Issac MS, Ashur W, Mousa H. Genetic polymorphisms of surfactant protein D rs2243639, interleukin (IL)-1beta rs16944 and IL-1RN rs2234663 in chronic obstructive pulmonary disease, healthy smokers, and non-smokers. Mol Diagn Ther (2014) 18:343–54.10.1007/s40291-014-0084-5
    1. Perez-Rubio G, Silva-Zolezzi I, Fernandez-Lopez JC, Camarena A, Velazquez-Uncal M, Morales-Mandujano F, et al. Genetic variants in IL6R and ADAM19 are associated with COPD severity in a Mexican Mestizo population. COPD (2016) 13(5):610–5.10.3109/15412555.2016.1161017
    1. Lock-Johansson S, Vestbo J, Sorensen G. Surfactant protein D, club cell protein 16, pulmonary and activation-regulated chemokine, C-reactive protein, and fibrinogen biomarker variation in chronic obstructive lung disease. Respir Res (2014) 15:147.10.1186/s12931-014-0147-5
    1. Obeidat M, Li X, Burgess S, Zhou G, Fishbane N, Hansel NN, et al. Surfactant protein D is a causal risk factor for COPD: results of Mendelian randomisation. Eur Respir J (2017) 50:1700657.10.1183/13993003.00657-2017
    1. Honda Y, Takahashi H, Kuroki Y, Akino T, Abe S. Decreased contents of surfactant proteins A and D in BAL fluids of healthy smokers. Chest (1996) 109:1006–9.10.1378/chest.109.4.1006
    1. Zou W, Liu S, Hu J, Sheng Q, He F, Li B, et al. Nicotine reduces the levels of surfactant proteins A and D via Wnt/beta-catenin and PKC signaling in human airway epithelial cells. Respir Physiol Neurobiol (2016) 221:1–10.10.1016/j.resp.2015.10.004
    1. Haddam N, Samira S, Dumont X, Taleb A, Haufroid V, Lison D, et al. Lung epithelium injury biomarkers in workers exposed to sulphur dioxide in a non-ferrous smelter. Biomarkers (2009) 14:292–8.10.1080/13547500902989088
    1. Stockfelt L, Sallsten G, Olin AC, Almerud P, Samuelsson L, Johannesson S, et al. Effects on airways of short-term exposure to two kinds of wood smoke in a chamber study of healthy humans. Inhal Toxicol (2012) 24:47–59.10.3109/08958378.2011.633281
    1. Kobayashi H, Kanoh S, Motoyoshi K. Serum surfactant protein-A, but not surfactant protein-D or KL-6, can predict preclinical lung damage induced by smoking. Biomarkers (2008) 13:385–92.10.1080/13547500801903651
    1. Ozyurek BA, Ulasli SS, Bozbas SS, Bayraktar N, Akcay S. Value of serum and induced sputum surfactant protein-D in chronic obstructive pulmonary disease. Multidiscip Respir Med (2013) 8:36.10.1186/2049-6958-8-36
    1. Ishikawa N, Hattori N, Kohno N, Kobayashi A, Hayamizu T, Johnson M. Airway inflammation in Japanese COPD patients compared with smoking and nonsmoking controls. Int J Chron Obstruct Pulmon Dis (2015) 10:185–92.10.2147/COPD.S74557
    1. Duffy S, Weir M, Criner GJ. The complex challenge of chronic obstructive pulmonary disease. Lancet Respir Med (2015) 3:917–9.10.1016/S2213-2600(15)00480-4
    1. Um SJ, Lam S, Coxson H, Man SF, Sin DD. Budesonide/formoterol enhances the expression of pro surfactant protein-B in lungs of COPD patients. PLoS One (2013) 8:e83881.10.1371/journal.pone.0083881
    1. Liu W, Ju CR, Chen RC, Liu ZG. Role of serum and induced sputum surfactant protein D in predicting the response to treatment in chronic obstructive pulmonary disease. Exp Ther Med (2014) 8:1313–7.10.3892/etm.2014.1865
    1. Ju CR, Liu W, Chen RC. Serum surfactant protein D: biomarker of chronic obstructive pulmonary disease. Dis Markers (2012) 32:281–7.10.3233/DMA-2011-0887
    1. Sin DD, Leung R, Gan WQ, Man SP. Circulating surfactant protein D as a potential lung-specific biomarker of health outcomes in COPD: a pilot study. BMC Pulm Med (2007) 7:13.10.1186/1471-2466-7-13
    1. Tkacova R, McWilliams A, Lam S, Sin DD. Integrating lung and plasma expression of pneumo-proteins in developing biomarkers in COPD: a case study of surfactant protein D. Med Sci Monit (2010) 16:CR540–4.
    1. El-Deek SE, Makhlouf HA, Saleem TH, Mandour MA, Mohamed NA. Surfactant protein D, soluble intercellular adhesion molecule-1 and high-sensitivity C-reactive protein as biomarkers of chronic obstructive pulmonary disease. Med Princ Pract (2013) 22:469–74.10.1159/000349934
    1. Zaky DSE, Naiem M, Eid HA, Adawy ZR, Abd-Elraheem SE, Mohamed ZAZ. Circulating surfactant protein D as a biomarker of severity in stable chronic pulmonary disease. Egypt J Chest Dis Tuberc (2014) 63:553–9.10.1016/j.ejcdt.2014.03.011
    1. Engstrom G, Lindberg C, Gerhardsson de Verdier M, Nihlen U, Anderson M, Svartengren M, et al. Blood biomarkers and measures of pulmonary function – a study from the Swedish twin registry. Respir Med (2012) 106:1250–7.10.1016/j.rmed.2012.05.004
    1. Lange P, Celli B, Agusti A, Boje Jensen G, Divo M, Faner R, et al. Lung-function trajectories leading to chronic obstructive pulmonary disease. N Engl J Med (2015) 373:111–22.10.1056/NEJMoa1411532
    1. Hoegh SV, Sorensen GL, Tornoe I, Lottenburger T, Ytting H, Nielsen HJ, et al. Long-term stability and circadian variation in circulating levels of surfactant protein D. Immunobiology (2010) 215:314–20.10.1016/j.imbio.2009.05.001
    1. Sin DD, Man SF, Marciniuk DD, Ford G, FitzGerald M, Wong E, et al. The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med (2008) 177:1207–14.10.1164/rccm.200709-1356OC
    1. Shakoori TA, Sin DD, Ghafoor F, Bashir S, Bokhari SN. Serum surfactant protein D during acute exacerbations of chronic obstructive pulmonary disease. Dis Markers (2009) 27:287–94.10.3233/DMA-2009-0674
    1. Zien Alaabden A, Mohammad Y, Fahoum S. The role of serum surfactant protein D as a biomarker of exacerbation of chronic obstructive pulmonary disease. Qatar Med J (2015) 2015:18.10.5339/qmj.2015.18
    1. Johansson SL, Roberts NB, Schlosser A, Andersen CB, Carlsen J, Wulf-Johansson H, et al. Microfibrillar-associated protein 4: a potential biomarker of chronic obstructive pulmonary disease. Respir Med (2014) 108:1336–44.10.1016/j.rmed.2014.06.003
    1. Labonte LE, Bourbeau J, Daskalopoulou SS, Zhang M, Coulombe P, Garland K, et al. Club cell-16 and RelB as novel determinants of arterial stiffness in exacerbating COPD patients. PLoS One (2016) 11:e0149974.10.1371/journal.pone.0149974
    1. Hurst JR, Vestbo J, Anzueto A, Locantore N, Mullerova H, Tal-Singer R, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med (2010) 363:1128–38.10.1056/NEJMoa0909883
    1. Coxson HO, Dirksen A, Edwards LD, Yates JC, Agusti A, Bakke P, et al. The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression: a prospective analysis from the ECLIPSE study. Lancet Respir Med (2013) 1:129–36.10.1016/S2213-2600(13)70006-7
    1. Kokuho N, Ishii T, Kamio K, Hayashi H, Kurahara M, Hattori K, et al. Diagnostic values for club cell secretory protein (CC16) in serum of patients of combined pulmonary fibrosis and emphysema. COPD (2015) 12:347–54.10.3109/15412555.2014.948994
    1. Nakano M, Omae K, Uchida K, Michikawa T, Yoshioka N, Hirata M, et al. Five-year cohort study: emphysematous progression of indium-exposed workers. Chest (2014) 146:1166–75.10.1378/chest.13-2484
    1. Vestbo J, Agusti A, Wouters EF, Bakke P, Calverley PM, Celli B, et al. Should we view chronic obstructive pulmonary disease differently after ECLIPSE? A clinical perspective from the study team. Am J Respir Crit Care Med (2014) 189:1022–30.10.1164/rccm.201311-2006PP
    1. Rennard SI, Locantore N, Delafont B, Tal-Singer R, Silverman EK, Vestbo J, et al. Identification of five chronic obstructive pulmonary disease subgroups with different prognoses in the ECLIPSE cohort using cluster analysis. Ann Am Thorac Soc (2015) 12:303–12.10.1513/AnnalsATS.201403-125OC
    1. Zemans RL, Jacobson S, Keene J, Kechris K, Miller BE, Tal-Singer R, et al. Multiple biomarkers predict disease severity, progression and mortality in COPD. Respir Res (2017) 18:117.10.1186/s12931-017-0597-7
    1. Groves AM, Gow AJ, Massa CB, Hall L, Laskin JD, Laskin DL. Age-related increases in ozone-induced injury and altered pulmonary mechanics in mice with progressive lung inflammation. Am J Physiol Lung Cell Mol Physiol (2013) 305:L555–68.10.1152/ajplung.00027.2013
    1. Ochs M, Knudsen L, Allen L, Stumbaugh A, Levitt S, Nyengaard JR, et al. GM-CSF mediates alveolar epithelial type II cell changes but not emphysema-like pathology in SP-D deficient mice. Am J Physiol Lung Cell Mol Physiol (2004) 287(6):L1333–41.10.1152/ajplung.00137.2004
    1. Knudsen L, Atochina-Vasserman EN, Massa CB, Birkelbach B, Guo CJ, Scott P, et al. The role of inducible nitric oxide synthase for interstitial remodeling of alveolar septa in surfactant protein D-deficient mice. Am J Physiol Lung Cell Mol Physiol (2015) 309:L959–69.10.1152/ajplung.00017.2015
    1. Schneider JP, Arkenau M, Knudsen L, Wedekind D, Ochs M. Lung remodeling in aging surfactant protein D deficient mice. Ann Anat (2017) 211:158–75.10.1016/j.aanat.2017.01.013
    1. Knudsen L, Wucherpfennig K, Mackay RM, Townsend P, Muhlfeld C, Richter J, et al. A recombinant fragment of human surfactant protein D lacking the short collagen-like stalk fails to correct morphological alterations in lungs of SP-D deficient mice. Anat Rec (Hoboken) (2009) 292:183–9.10.1002/ar.20830
    1. Pilecki B, Wulf-Johansson H, Støttrup C, Jørgensen PT, Schlosser A, Hansen S, et al. Surfactant protein D deficiency aggravates cigarette smoke-induced inflammation. Abstract. Scand J Immunol (2016) 83:375–6.10.1111/sji.12431
    1. Haanes KA, Kruse LS, Wulf-Johansson H, Stottrup CC, Sorensen GL, Edvinsson L. Contractile changes in the vasculature after subchronic smoking: a comparison between wild type and surfactant protein D knock-out mice. Nicotine Tob Res (2016) 18:642–6.10.1093/ntr/ntv243
    1. Kierstein S, Poulain FR, Cao Y, Grous M, Mathias R, Kierstein G, et al. Susceptibility to ozone-induced airway inflammation is associated with decreased levels of surfactant protein D. Respir Res (2006) 7:85.10.1186/1465-9921-7-85
    1. Mikura S, Wada H, Higaki M, Yasutake T, Ishii H, Kamiya S, et al. Erythromycin prevents the pulmonary inflammation induced by exposure to cigarette smoke. Transl Res (2011) 158:30–7.10.1016/j.trsl.2011.03.001
    1. Connor AJ, Laskin JD, Laskin DL. Ozone-induced lung injury and sterile inflammation. Role of toll-like receptor 4. Exp Mol Pathol (2012) 92:229–35.10.1016/j.yexmp.2012.01.004
    1. Horie M, Fukui H, Endoh S, Maru J, Miyauchi A, Shichiri M, et al. Comparison of acute oxidative stress on rat lung induced by nano and fine-scale, soluble and insoluble metal oxide particles: NiO and TiO2. Inhal Toxicol (2012) 24:391–400.10.3109/08958378.2012.682321
    1. Lee YS, Chen PW, Tsai PJ, Su SH, Liao PC. Proteomics analysis revealed changes in rat bronchoalveolar lavage fluid proteins associated with oil mist exposure. Proteomics (2006) 6:2236–50.10.1002/pmic.200500347
    1. Brusselle GG, Joos GF, Bracke KR. New insights into the immunology of chronic obstructive pulmonary disease. Lancet (2011) 378:1015–26.10.1016/S0140-6736(11)60988-4
    1. Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol (2008) 8:183–92.10.1038/nri2254
    1. Groves AM, Gow AJ, Massa CB, Laskin JD, Laskin DL. Prolonged injury and altered lung function after ozone inhalation in mice with chronic lung inflammation. Am J Respir Cell Mol Biol (2012) 47:776–83.10.1165/rcmb.2011-0433OC
    1. Bridges JP, Davis HW, Damodarasamy M, Kuroki Y, Howles G, Hui DY, et al. Pulmonary surfactant proteins A and D are potent endogenous inhibitors of lipid peroxidation and oxidative cellular injury. J Biol Chem (2000) 275:38848–55.10.1074/jbc.M005322200
    1. Atochina EN, Beers MF, Hawgood S, Poulain F, Davis C, Fusaro T, et al. Surfactant protein-D, a mediator of innate lung immunity, alters the products of nitric oxide metabolism. Am J Respir Cell Mol Biol (2004) 30:271–9.10.1165/rcmb.2003-0091OC
    1. Atochina-Vasserman EN, Beers MF, Kadire H, Tomer Y, Inch A, Scott P, et al. Selective inhibition of inducible NO synthase activity in vivo reverses inflammatory abnormalities in surfactant protein D-deficient mice. J Immunol (2007) 179:8090–7.10.4049/jimmunol.179.12.8090
    1. Knudsen L, Atochina-Vasserman EN, Guo CJ, Scott PA, Haenni B, Beers MF, et al. NOS2 is critical to the development of emphysema in Sftpd deficient mice but does not affect surfactant homeostasis. PLoS One (2014) 9:e85722.10.1371/journal.pone.0085722
    1. Korfhagen TR, Sheftelyevich V, Burhans MS, Bruno MD, Ross GF, Wert SE, et al. Surfactant protein-D regulates surfactant phospholipid homeostasis in vivo. J Biol Chem (1998) 273:28438–43.10.1074/jbc.273.43.28438
    1. Vandivier RW, Ogden CA, Fadok VA, Hoffmann PR, Brown KK, Botto M, et al. Role of surfactant proteins A, D, and C1q in the clearance of apoptotic cells in vivo and in vitro: calreticulin and CD91 as a common collectin receptor complex. J Immunol (2002) 169:3978–86.10.4049/jimmunol.169.7.3978
    1. Ariestanti DM, Ando H, Hirose S, Nakamura N. Targeted disruption of Ig-Hepta/Gpr116 causes emphysema-like symptoms that are associated with alveolar macrophage activation. J Biol Chem (2015) 290:11032–40.10.1074/jbc.M115.648311
    1. Bridges JP, Ludwig MG, Mueller M, Kinzel B, Sato A, Xu Y, et al. Orphan G protein-coupled receptor GPR116 regulates pulmonary surfactant pool size. Am J Respir Cell Mol Biol (2013) 49:348–57.10.1165/rcmb.2012-0439OC
    1. Yang MY, Hilton MB, Seaman S, Haines DC, Nagashima K, Burks CM, et al. Essential regulation of lung surfactant homeostasis by the orphan G protein-coupled receptor GPR116. Cell Rep (2013) 3:1457–64.10.1016/j.celrep.2013.04.019
    1. Ryu JH, Myers JL, Swensen SJ. Bronchiolar disorders. Am J Respir Crit Care Med (2003) 168:1277–92.10.1164/rccm.200301-053SO
    1. Whitsett JA, Wert SE, Weaver TE. Diseases of pulmonary surfactant homeostasis. Annu Rev Pathol (2015) 10:371–93.10.1146/annurev-pathol-012513-104644
    1. Hughes DA, Haslam PL. Effect of smoking on the lipid composition of lung lining fluid and relationship between immunostimulatory lipids, inflammatory cells and foamy macrophages in extrinsic allergic alveolitis. Eur Respir J (1990) 3:1128–39.
    1. Kitamura T, Tanaka N, Watanabe J, Uchida K, Kanegasaki S, Yamada Y, et al. Idiopathic pulmonary alveolar proteinosis as an autoimmune disease with neutralizing antibody against granulocyte/macrophage colony-stimulating factor. J Exp Med (1999) 190:875–80.10.1084/jem.190.6.875
    1. Hoegh SV, Lindegaard HM, Sorensen GL, Hoj A, Bendixen C, Junker P, et al. Circulating surfactant protein D is decreased in early rheumatoid arthritis: a 1-year prospective study. Scand J Immunol (2008) 67:71–6.10.1111/j.1365-3083.2007.02039.x
    1. Hoegh SV, Voss A, Sorensen GL, Hoj A, Bendixen C, Junker P, et al. Circulating surfactant protein D is decreased in systemic lupus erythematosus. J Rheumatol (2009) 36:2449–53.10.3899/jrheum.090069
    1. Christensen AF, Sorensen GL, Horslev-Petersen K, Holmskov U, Lindegaard HM, Junker K, et al. Circulating surfactant protein-D is low and correlates negatively with systemic inflammation in early, untreated rheumatoid arthritis. Arthritis Res Ther (2010) 12:R39.10.1186/ar2948
    1. Christensen AF, Hoegh SV, Lottenburger T, Holmskov U, Tornoe I, Horslev-Petersen K, et al. Circadian rhythm and the influence of physical activity on circulating surfactant protein D in early and long-standing rheumatoid arthritis. Rheumatol Int (2011) 31:1617–23.10.1007/s00296-010-1538-7
    1. Fernández-Real JM, Valdes S, Manco M, Chico B, Botas P, Campo A, et al. Surfactant protein D, a marker of lung innate immunity, is positively associated with insulin sensitivity. Diabetes Care (2010) 33:847–53.10.2337/dc09-0542
    1. Tanaka M, Arimura Y, Goto A, Hosokawa M, Nagaishi K, Yamashita K, et al. Genetic variants in surfactant, pulmonary-associated protein D (SFTPD) and Japanese susceptibility to ulcerative colitis. Inflamm Bowel Dis (2009) 15:918–25.10.1002/ibd.20936
    1. Hill J, Heslop C, Man SF, Frohlich J, Connett JE, Anthonisen NR, et al. Circulating surfactant protein-D and the risk of cardiovascular morbidity and mortality. Eur Heart J (2011) 32:1918–25.10.1093/eurheartj/ehr124
    1. Doyle TJ, Patel AS, Hatabu H, Nishino M, Wu G, Osorio JC, et al. Detection of rheumatoid arthritis-interstitial lung disease is enhanced by serum biomarkers. Am J Respir Crit Care Med (2015) 191:1403–12.10.1164/rccm.201411-1950OC
    1. Curkendall SM, Lanes S, de Luise C, Stang MR, Jones JK, She D, et al. Chronic obstructive pulmonary disease severity and cardiovascular outcomes. Eur J Epidemiol (2006) 21:803–13.10.1007/s10654-006-9066-1
    1. Williams MC, Murchison JT, Edwards LD, Agusti A, Bakke P, Calverley PM, et al. Coronary artery calcification is increased in patients with COPD and associated with increased morbidity and mortality. Thorax (2014) 69:718–23.10.1136/thoraxjnl-2012-203151
    1. Gargiulo P, Banfi C, Ghilardi S, Magri D, Giovannardi M, Bonomi A, et al. Surfactant-derived proteins as markers of alveolar membrane damage in heart failure. PLoS One (2014) 9:e115030.10.1371/journal.pone.0115030
    1. Kati C, Alacam H, Duran L, Guzel A, Akdemir HU, Sisman B, et al. The effectiveness of the serum surfactant protein D (Sp-D) level to indicate lung injury in pulmonary embolism. Clin Lab (2014) 60:1457–64.10.7754/Clin.Lab.2013.131009
    1. Heimer SR, Evans DJ, Mun JJ, Stern ME, Fleiszig SM. Surfactant protein D contributes to ocular defense against Pseudomonas aeruginosa in a murine model of dry eye disease. PLoS One (2013) 8:e65797.10.1371/journal.pone.0065797
    1. Liu Z, Shi Q, Liu J, Abdel-Razek O, Xu Y, Cooney RN, et al. Innate immune molecule surfactant protein D attenuates sepsis-induced acute pancreatic injury through modulating apoptosis and NF-kappaB-mediated inflammation. Sci Rep (2015) 5:17798.10.1038/srep17798
    1. Liu J, Abdel-Razek O, Liu Z, Hu F, Zhou Q, Cooney RN, et al. Role of surfactant proteins A and D in sepsis-induced acute kidney injury. Shock (2015) 43:31–8.10.1097/SHK.0000000000000270
    1. Hu F, Ding G, Zhang Z, Gatto LA, Hawgood S, Poulain FR, et al. Innate immunity of surfactant proteins A and D in urinary tract infection with uropathogenic Escherichia coli. Innate Immun (2016) 22:9–20.10.1177/1753425915609973
    1. Murray E, Khamri W, Walker MM, Eggleton P, Moran AP, Ferris JA, et al. Expression of surfactant protein D in the human gastric mucosa and during Helicobacter pylori infection. Infect Immun (2002) 70:1481–7.10.1128/IAI.70.3.1481-1487.2002
    1. Khamri W, Worku ML, Anderson AE, Walker MM, Hawgood S, Reid KB, et al. Helicobacter infection in the surfactant protein D-deficient mouse. Helicobacter (2007) 12:112–23.10.1111/j.1523-5378.2007.00480.x
    1. Du X, Meng Q, Sharif A, Abdel-Razek OA, Zhang L, Wang G, et al. Surfactant proteins SP-A and SP-D ameliorate pneumonia severity and intestinal injury in a murine model of Staphylococcus aureus pneumonia. Shock (2016) 46(2):164–72.10.1097/SHK.0000000000000587
    1. Zhang L, Meng Q, Yepuri N, Wang G, Xi X, Cooney RN. Surfactant proteins-A and -D attenuate LPS-induced apoptosis in primary intestinal epithelial cells (IECs). Shock (2017) 49(1):90–98.10.1371/journal.pone.0174441
    1. Madhukaran SP, Koippallil Gopalakrishnan AR, Pandit H, Marri ED, Kouser L, Jamil K, et al. Expression of surfactant proteins SP-A and SP-D in murine decidua and immunomodulatory effects on decidual macrophages. Immunobiology (2016) 221:377–86.10.1016/j.imbio.2015.09.019
    1. Wulf-Johansson H, Thinggaard M, Tan Q, Johansson SL, Schlosser A, Christensen K, et al. Circulating surfactant protein D is associated to mortality in elderly women: a twin study. Immunobiology (2013) 218:712–7.10.1016/j.imbio.2012.08.272
    1. Nybo M, Andersen K, Sorensen GL, Lolk A, Kragh-Sorensen P, Holmskov U. Serum surfactant protein D is correlated to development of dementia and augmented mortality. Clin Immunol (2007) 123:333–7.10.1016/j.clim.2007.03.001
    1. Anthonisen NR, Connett JE, Enright PL, Manfreda J, Lung Health Study Research Group . Hospitalizations and mortality in the lung health study. Am J Respir Crit Care Med (2002) 166:333–9.10.1164/rccm.2110093
    1. Hansell AL, Walk JA, Soriano JB. What do chronic obstructive pulmonary disease patients die from? A multiple cause coding analysis. Eur Respir J (2003) 22:809–14.10.1183/09031936.03.00031403
    1. Sin DD, Wu L, Man SF. The relationship between reduced lung function and cardiovascular mortality: a population-based study and a systematic review of the literature. Chest (2005) 127:1952–9.10.1378/chest.127.6.1952
    1. Curkendall SM, DeLuise C, Jones JK, Lanes S, Stang MR, Goehring E, Jr, et al. Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients. Ann Epidemiol (2006) 16:63–70.10.1016/j.annepidem.2005.04.008
    1. Finkelstein J, Cha E, Scharf SM. Chronic obstructive pulmonary disease as an independent risk factor for cardiovascular morbidity. Int J Chron Obstruct Pulmon Dis (2009) 4:337–49.10.2147/COPD.S6400
    1. Fisher KA, Stefan MS, Darling C, Lessard D, Goldberg RJ. Impact of COPD on the mortality and treatment of patients hospitalized with acute decompensated heart failure: the Worcester Heart Failure study. Chest (2015) 147:637–45.10.1378/chest.14-0607
    1. Hu F, Zhong Q, Gong J, Qin Y, Cui L, Yuan H. Serum surfactant protein D is associated with atherosclerosis of the carotid artery in patients on maintenance hemodialysis. Clin Lab (2016) 62:97–104.10.7754/Clin.Lab.2015.150536
    1. Merck E, Gaillard C, Scuiller M, Scapini P, Cassatella MA, Trinchieri G, et al. Ligation of the FcR gamma chain-associated human osteoclast-associated receptor enhances the proinflammatory responses of human monocytes and neutrophils. J Immunol (2006) 176:3149–56.10.4049/jimmunol.176.5.3149
    1. Merck E, Gaillard C, Gorman DM, Montero-Julian F, Durand I, Zurawski SM, et al. OSCAR is an FcRgamma-associated receptor that is expressed by myeloid cells and is involved in antigen presentation and activation of human dendritic cells. Blood (2004) 104:1386–95.10.1182/blood-2004-03-0850
    1. Merck E, de Saint-Vis B, Scuiller M, Gaillard C, Caux C, Trinchieri G, et al. Fc receptor gamma-chain activation via hOSCAR induces survival and maturation of dendritic cells and modulates toll-like receptor responses. Blood (2005) 105:3623–32.10.1182/blood-2004-07-2809
    1. Goettsch C, Rauner M, Sinningen K, Helas S, Al-Fakhri N, Nemeth K, et al. The osteoclast-associated receptor (OSCAR) is a novel receptor regulated by oxidized low-density lipoprotein in human endothelial cells. Endocrinology (2011) 152:4915–26.10.1210/en.2011-1282
    1. Hirano Y, Choi A, Tsuruta M, Jaw JE, Oh Y, Ngan D, et al. Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice. Cardiovasc Res (2017) 113:1208–18.10.1093/cvr/cvx067
    1. Skaggs BJ, Hahn BH, McMahon M. Accelerated atherosclerosis in patients with SLE – mechanisms and management. Nat Rev Rheumatol (2012) 8:214–23.10.1038/nrrheum.2012.14
    1. Lazarus R, Sparrow D, Weiss ST. Baseline ventilatory function predicts the development of higher levels of fasting insulin and fasting insulin resistance index: the Normative Aging study. Eur Respir J (1998) 12:641–5.10.1183/09031936.98.12030641
    1. Agusti A, Calverley PM, Celli B, Coxson HO, Edwards LD, Lomas DA, et al. Characterisation of COPD heterogeneity in the ECLIPSE cohort. Respir Res (2010) 11:122.10.1186/1465-9921-11-122
    1. Song Y, Klevak A, Manson JE, Buring JE, Liu S. Asthma, chronic obstructive pulmonary disease, and type 2 diabetes in the women’s health study. Diabetes Res Clin Pract (2010) 90:365–71.10.1016/j.diabres.2010.09.010
    1. Divo M, Cote C, de Torres JP, Casanova C, Marin JM, Pinto-Plata V, et al. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med (2012) 186:155–61.10.1164/rccm.201201-0034OC
    1. Wannamethee SG, Shaper AG, Rumley A, Sattar N, Whincup PH, Thomas MC, et al. Lung function and risk of type 2 diabetes and fatal and nonfatal major coronary heart disease events: possible associations with inflammation. Diabetes Care (2010) 33:1990–6.10.2337/dc10-0324
    1. Kinney GL, Black-Shinn JL, Wan ES, Make B, Regan E, Lutz S, et al. Pulmonary function reduction in diabetes with and without chronic obstructive pulmonary disease. Diabetes Care (2014) 37:389–95.10.2337/dc13-1435
    1. Fernández-Real JM, Pickup JC. Innate immunity, insulin resistance and type 2 diabetes. Trends Endocrinol Metab (2008) 19:10–6.10.1016/j.tem.2007.10.004
    1. Yeh HC, Punjabi NM, Wang NY, Pankow JS, Duncan BB, Brancati FL. Vital capacity as a predictor of incident type 2 diabetes: the atherosclerosis risk in communities study. Diabetes Care (2005) 28:1472–9.10.2337/diacare.28.6.1472
    1. Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature (2006) 444:881–7.10.1038/nature05488
    1. Yeh F, Dixon AE, Marion S, Schaefer C, Zhang Y, Best LG, et al. Obesity in adults is associated with reduced lung function in metabolic syndrome and diabetes: the strong heart study. Diabetes Care (2011) 34:2306–13.10.2337/dc11-0682
    1. Lackey DE, Olefsky JM. Regulation of metabolism by the innate immune system. Nat Rev Endocrinol (2016) 12:15–28.10.1038/nrendo.2015.189
    1. Bottai M, Pistelli F, Di Pede F, Carrozzi L, Baldacci S, Matteelli G, et al. Longitudinal changes of body mass index, spirometry and diffusion in a general population. Eur Respir J (2002) 20:665–73.10.1183/09031936.02.01282001
    1. Lin WY, Yao CA, Wang HC, Huang KC. Impaired lung function is associated with obesity and metabolic syndrome in adults. Obesity (Silver Spring) (2006) 14:1654–61.10.1038/oby.2006.190
    1. Leone N, Courbon D, Thomas F, Bean K, Jego B, Leynaert B, et al. Lung function impairment and metabolic syndrome: the critical role of abdominal obesity. Am J Respir Crit Care Med (2009) 179:509–16.10.1164/rccm.200807-1195OC
    1. van Huisstede A, Cabezas MC, Birnie E, van de Geijn GJ, Rudolphus A, Mannaerts G, et al. Systemic inflammation and lung function impairment in morbidly obese subjects with the metabolic syndrome. J Obes (2013) 2013:131349.10.1155/2013/131349
    1. Naveed B, Weiden MD, Kwon S, Gracely EJ, Comfort AL, Ferrier N, et al. Metabolic syndrome biomarkers predict lung function impairment: a nested case-control study. Am J Respir Crit Care Med (2012) 185:392–9.10.1164/rccm.201109-1672OC
    1. López-Cano C, Lecube A, Garcia-Ramirez M, Munoz X, Sanchez E, Seminario A, et al. Serum surfactant protein D as a biomarker for measuring lung involvement in obese patients with type 2 diabetes. J Clin Endocrinol Metab (2017) 102:4109–16.10.1210/jc.2017-00913
    1. Sorensen GL, Hjelmborg JV, Leth-Larsen R, Schmidt V, Fenger M, Poulain F, et al. Surfactant protein D of the innate immune defence is inversely associated with human obesity and SP-D deficiency infers increased body weight in mice. Scand J Immunol (2006) 64:633–8.10.1111/j.1365-3083.2006.01853.x
    1. Stapleton RD, Dixon AE, Parsons PE, Ware LB, Suratt BT, NHLBI Acute Respiratory Distress Syndrome Network . The association between BMI and plasma cytokine levels in patients with acute lung injury. Chest (2010) 138:568–77.10.1378/chest.10-0014
    1. Stidsen JV, Khorooshi R, Rahbek MK, Kirketerp-Moller KL, Hansen PB, Bie P, et al. Surfactant protein D deficiency in mice is associated with hyperphagia, altered fat deposition, insulin resistance, and increased basal endotoxemia. PLoS One (2012) 7:e35066.10.1371/journal.pone.0035066
    1. DeSilva NS, Ofek I, Crouch EC. Interactions of surfactant protein D with fatty acids. Am J Respir Cell Mol Biol (2003) 29:757–70.10.1165/rcmb.2003-0186OC
    1. Layden BT, Durai V, Newman MV, Marinelarena AM, Ahn CW, Feng G, et al. Regulation of pancreatic islet gene expression in mouse islets by pregnancy. J Endocrinol (2010) 207:265–79.10.1677/JOE-10-0298
    1. Aye T, Toschi E, Sharma A, Sgroi D, Bonner-Weir S. Identification of markers for newly formed beta-cells in the perinatal period: a time of recognized beta-cell immaturity. J Histochem Cytochem (2010) 58:369–76.10.1369/jhc.2009.954909
    1. Trevino-Alanis M, Ventura-Juarez J, Hernandez-Pinero J, Nevarez-Garza A, Quintanar-Stephano A, Gonzalez-Pina A. Delayed lung maturation of foetus of diabetic mother rats develop with a diminish, but without changes in the proportion of type I and II pneumocytes, and decreased expression of protein D-associated surfactant factor. Anat Histol Embryol (2009) 38:169–76.10.1111/j.1439-0264.2008.00902.x
    1. Reading PC, Allison J, Crouch EC, Anders EM. Increased susceptibility of diabetic mice to influenza virus infection: compromise of collectin-mediated host defense of the lung by glucose? J Virol (1998) 72:6884–7.
    1. Seong SY, Matzinger P. Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses. Nat Rev Immunol (2004) 4:469–78.10.1038/nri1372
    1. Bihlet AR, Karsdal MA, Bay-Jensen AC, Read S, Kristensen JH, Sand JM, et al. Clinical drug development using dynamic biomarkers to enable personalized health care in COPD. Chest (2015) 148:16–23.10.1378/chest.15-0296
    1. Jenkins RG, Simpson JK, Saini G, Bentley JH, Russell AM, Braybrooke R, et al. Longitudinal change in collagen degradation biomarkers in idiopathic pulmonary fibrosis: an analysis from the prospective, multicentre PROFILE study. Lancet Respir Med (2015) 3:462–72.10.1016/S2213-2600(15)00048-X
    1. Nagae H, Takahashi H, Kuroki Y, Honda Y, Nagata A, Ogasawara Y, et al. Enzyme-linked immunosorbent assay using F(ab’)2 fragment for the detection of human pulmonary surfactant protein D in sera. Clin Chim Acta (1997) 266:157–71.10.1016/S0009-8981(97)00124-1
    1. Nikolaidis NM, White MR, Allen K, Tripathi S, Qi L, McDonald B, et al. Mutations flanking the carbohydrate binding site of surfactant protein D confer antiviral activity for pandemic influenza A viruses. Am J Physiol Lung Cell Mol Physiol (2014) 306:L1036–44.10.1152/ajplung.00035.2014
    1. van Eijk M, Bruinsma L, Hartshorn KL, White MR, Rynkiewicz MJ, Seaton BA, et al. Introduction of N-linked glycans in the lectin domain of surfactant protein D: impact on interactions with influenza A viruses. J Biol Chem (2011) 286:20137–51.10.1074/jbc.M111.224469
    1. Reinhardt A, Wehle M, Geissner A, Crouch EC, Kang Y, Yang Y, et al. Structure binding relationship of human surfactant protein D and various lipopolysaccharide inner core structures. J Struct Biol (2016) 195:387–95.10.1016/j.jsb.2016.06.019
    1. Gram K, Yang S, Steiner M, Somani A, Hawgood S, Blazar BR, et al. Simultaneous absence of surfactant proteins A and D increases lung inflammation and injury after allogeneic HSCT in mice. Am J Physiol Lung Cell Mol Physiol (2009) 296:L167–75.10.1152/ajplung.90253.2008
    1. Thacker S, Moran A, Lionakis M, Mastrangelo MA, Halder T, del Pilar Huby M, et al. Restoration of lung surfactant protein D by IL-6 protects against secondary pneumonia following hemorrhagic shock. J Infect (2014) 68:231–41.10.1016/j.jinf.2013.11.010
    1. White J, Ikegami M. Surfactant Protein D for the Treatment Of Disorders Associated with Lung Injury. US20110189104. Cincinatti (OH) US: (2011).
    1. Clark H, Nadesalingam P, Reid KBM, Strong P. Recombinant Surfactant Protein D Compositions and Methods of Use Thereof. US20120010126. Southhampton GB: (2012).
    1. Hess G, Horsh A, Zdunek D. Surfactant Proteins B and D for Differential Diagnosis of Dyspnea. US20100261283. Basel (CH) (2010).
    1. Panettieri RA, Beers MF, Haczku AF, Sims MW. Surfactant Protein D Is a Biomarker for Steroid Responsiveness in Asthma and Chronic Obstructive Pulmonary Disease. US201001143920. Pennsylvania: (2010).
    1. Zhang L, Zhang W, Xu J, Yang S. Use of Glycyrrhetinic Acid, Glycyrrhizic Acid and Related Compounds for Prevention and/or Treatment of Pulmonary Fibrosis. US20120053141. Gainesville FL US: (2012).
    1. Mahajan L, Madan T, Sarma PU, Kishore U. Human Lung Surfactant Protein, SP-D, Modulates Eosinophil Activation and Survival and Enhances Phagocytosis of Apoptotic Basophils. US20080255043. Delhi (In) (2008).
    1. Shteyngart B. Intratracheal Administration of Lysozyme with Other Therapeutic Agents in the Prevention and Treatment of Respiratory Disorders. US 20050271645 A1. Brooklyn NY US: (2005).
    1. Chang C-H, Goldenberg DM, McBride WJ, Rossi EA. Stably Tethered Structures of Defined Compositions with Multiple Functions or Binding Specificities. Patent Application Number 20150050715. Morris Planes NJ US: (2009).

Source: PubMed

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