Neutrophils in periodontal inflammation

David A Scott, Jennifer Krauss, David A Scott, Jennifer Krauss

Abstract

Neutrophils (also called polymorphonuclear leukocytes) are the most abundant leukocytes whose primary purpose as anti-microbial professional phagocytes is to kill extracellular pathogens. Neutrophils and macrophages are phagocytic cell types that along with other cells effectively link the innate and adaptive arms of the immune response, and help promote inflammatory resolution and tissue healing. Found extensively within the gingival crevice and epithelium, neutrophils are considered the key protective cell type in the periodontal tissues. Histopathology of periodontal lesions indicates that neutrophils form a 'wall' between the junctional epithelium and the pathogen-rich dental plaque which functions as a robust anti-microbial secretory structure and as a unified phagocytic apparatus. However, neutrophil protection is not without cost and is always considered a two-edged sword in that overactivity of neutrophils can cause tissue damage and prolong the extent and severity of inflammatory periodontal diseases. This review will cover the innate and inflammatory functions of neutrophils, and describe the importance and utility of neutrophils to the host response and the integrity of the periodontium in health and disease.

Copyright © 2012 S. Karger AG, Basel.

Figures

Figure 1. Interface of bacterial plaque and…
Figure 1. Interface of bacterial plaque and crevicular neutrophils within the periodontal pocket
Neutrophils in the periodontal pocket forming a wall against the plaque biofilm. Neutrophils cannot engulf the large biofilm structure in vivo. The formation of a wall against the biofilm may be a protective mechanism. Nevertheless, an attempt is made to engulf the surface layer of this biofilm (yellow arrows). During this process of frustrated phagocytosis, enzymes within neutrophil lysosomal granules (red arrows), products of the oxidative burst, and other pro-inflammatory substances may be released directly into the pocket and/or the underlying tissue, where they have a predominantly destructive effect. Figure and text reproduced with permission, from(3).
Figure 2. T.E.M. image of a typical…
Figure 2. T.E.M. image of a typical human neutrophil
The multi-lobed nucleus and granule-dense cytoplasm are clearly apparent. Scale bar represents 2 μM. The image is taken from a manuscript currently under consideration for publication by Cell Death and Disease (14).
Figure 3. Contents of the intracellular membrane-bound…
Figure 3. Contents of the intracellular membrane-bound compartments of human neutrophils
aCD63 and CD68 are degranulation markers; bProteinase 3; cVAMP2 is key in granule membrane-cell membrane fusion and exocytosis; dNADPH oxidase subunits involved in ROS production (Gp91phox; p22phox); eTLR1, -2, -4, -6 and -8; fCRCX1, -2 and -4 as well as chemokine receptors 1, -2 and -3; gcomplement receptor 1 (CD35), c1qR. Data presented in Figure 3 are combined from (, –13, 15).
Figure 4. Extracellular neutrophil traps (NETs) in…
Figure 4. Extracellular neutrophil traps (NETs) in the periodontitis
TEMs of pocket epithelium biopsies are presented. (A) Overview of neutrophil extracellular traps on the pocket epithelium surface. The pronounced blackening is characteristic for neutrophil extracellular traps. The open arrows indicate neutrophil extracellular traps threads. (B) Detail of (A). The threads (open arrows) consist of individual fibers that run in parallel. (C) High magnification reveals that neutrophil extracellular traps consist of uniformly thick fibers (small solid arrows) with a diameter of nearly 15–17 nm. (D) Solitary bacteria (indicated by solid white arrowheads) entrapped by crevicular neutrophil extracellular traps. (E) A bacterium (solid white arrowhead) adherent to the epithelium surface is entrapped by neutrophil extracellular traps. A longitudinally running neutrophil extracellular trap fiber is delineated with white bars. Small solid white arrows: a multitude of cross-sectioned neutrophil extracellular trap fibers. (F) A scheme of a crevice. On the left: an epithelial cell with an adherent bacterium and bacteria in different stages of internalization. In the middle: periodontal crevice. Neutrophil extracellular traps build a ‘firewall’, protecting the gingiva from bacteria dispersing out of the subgingival plaque. The neutrophil extracellular traps, together with the entrapped bacteria, are continuously pushed into the oral cavity by the crevicular exudate outflow. Open white arrow: direction of the crevicular exudate outflow. On the right: subgingival plaque. Solid black arrow: a bacterium dispersing from the subgingival plaque. Figure and text reproduced, with permission, from (39).
Figure 5. Periodontal manifestations of Papillon-Lefevre syndrome
Figure 5. Periodontal manifestations of Papillon-Lefevre syndrome
A and B, Photographs showing marked red inflamed and swollen gingivae. C and D, Radiograph showing severe loss of alveolar bone. Images reproduced, with permission, from (139).
Figure 6. Promyelocytic and neutrophilic HL-60 cells…
Figure 6. Promyelocytic and neutrophilic HL-60 cells express α7- nicotinic acetylcholine receptors
A. α7 nAChR Western blot: Lane 1. Mouse frontal brain extract (10 μg; positive control); Lane 2. Lysate (40 μg) of promyelocytic HL-60 cells; Lanes 3 to 5. Lysate (40 μg) of five day, DMSO-induced (neutrophilic) HL-60 cells without nicotine, or with 10−6 M nicotine, or with 10−4 M nicotine treatment, respectively. α7 nAChR-specific antibodies (Santa Cruz SC-5544) bound to protein bands exhibiting a relative molecular mass of 55.0 KDa in all lanes. Densitometric analysis (data not shown) revealed that α7 nAChR-specific band intensities were significantly increased in the DMSO-treated samples, relative to promyelocytic cells (n = 5, *p < 0.05), but that this differentiation-associated increase α7 nAChR protein level was not influenced by nicotine exposure during differentiation in any statistically significant manner. B. α7 nAChR Immunofluorescence staining (x1000): Fixed five-day, DMSO-induced HL-60 cells were incubated with a polyclonal rabbit anti-α7 antibody (Santa Cruz SC-5544) before staining with a FITC-conjugated anti-rabbit antibody (Santa Cruz SC-2253). α7 nAChR-specific staining was evenly distributed across the cells. A similar cellular distribution of α7 nAChR was observed in promyelocytic cells (data not shown). C. Negative control for α7 nAChR Immunofluorescence staining (x1000). This figure was originally published by BioMed Central in (148).
Figure 7. Consequences of α7 nicotinic acetylcholine…
Figure 7. Consequences of α7 nicotinic acetylcholine receptor engagement by various agonists in innate cells
The α7 acetylcholine receptor-initiated anti-inflammatory pathway can be stimulated by various stimuli. The endogenous innate cell α7nAChR ligand is acetylcholine that is produced by the vagus system in response to infection or other tissue insult (–172). The function of acetylcholine release is to limit an overly exuberant cytokine response to infection. Many therapeutic agents are under development that attempt to take advantage of this suppressive pathway (173). Eventually, such drugs may prove efficacious in the treatment of multiple inflammatory diseases and conditions, including septic shock, pancreatitis and inflammatory bowel diseases, as well as periodontitis (–176). Cigarette smoke contains large amounts of a potent, exogenous α7nAChR agonist, nicotine (–178) (163). The primary stable metabolite of nicotine, cotinine, is also an efficient α7nAChR agonist (179). The consequences of α7nAChR engagement by acetylcholine, pharmaceutical agents or nicotine/cotinine is a suppression of the inflammatory response (, , –180). When triggered at the appropriate time, α7nAChR engagement would normally be beneficial. In the case of nicotine, it has been shown that α7nAChR engagement also results in the suppression of the oxidative burst (148, 181), a critical bacterial killing mechanism in phagocytic innate cells. Furthermore, nicotine-α7nAChR interactions may also stimulate the rapid release of matrix metalloproteinases and other proteolytic enzymes (148) (152) (182) from innate cells. Therefore, chronic, inappropriate nicotinic stimulation of innate α7nAChRs in smokers may increase susceptibility to infection with periodontal pathogens by supressing the inflammatory response and phagocytic killing required to fight infection. Additionally, increased protease release from nicotine-exposed innate cells may promote protease-protease inhibitor imbalances that contribute to the tissue remodelling apparent in periodontal diseases (183). Figure reproduced and text adapted from (146).

References

    1. Meng H, Xu L, Li Q, Han J, Zhao Y. Determinants of host susceptibility in aggressive periodontitis. Periodontol 2000. 2007;43:133–59. doi: 10.1111/j.1600-0757.2006.00204.x. PRD204 [pii]
    1. Schenkein HA. Host responses in maintaining periodontal health and determining periodontal disease. Periodontol 2000. 2006;40:77–93. doi: 10.1111/j.1600-0757.2005.00144.x. PRD144 [pii]
    1. Ryder MI. Comparison of neutrophil functions in aggressive and chronic periodontitis. Periodontol 2000. 2010;53:124–37. doi: 10.1111/j.1600-0757.2009.00327.x. PRD327 [pii]
    1. Deas DE, Mackey SA, McDonnell HT. Systemic disease and periodontitis: manifestations of neutrophil dysfunction. Periodontol 2000. 2003;32:82–104.
    1. Bender JS, Thang H, Glogauer M. Novel rinse assay for the quantification of oral neutrophils and the monitoring of chronic periodontal disease. J Periodontal Res. 2006;41(3):214–20. doi: 10.1111/j.1600-0765.2005.00861.x. JRE861 [pii]
    1. Liu RK, Cao CF, Meng HX, Gao Y. Polymorphonuclear neutrophils and their mediators in gingival tissues from generalized aggressive periodontitis. J Periodontol. 2001;72(11):1545–53. doi: 10.1902/jop.2001.72.11.1545.
    1. Andersen E, Cimasoni G. A rapid and simple method for counting crevicular polymorphonuclear leucocytes. J Clin Periodontol. 1993;20(9):651–5.
    1. Borregaard N, Sorensen OE, Theilgaard-Monch K. Neutrophil granules: a library of innate immunity proteins. Trends Immunol. 2007;28(8):340–5. doi: 10.1016/j.it.2007.06.002. S1471-4906(07)00156-1 [pii]
    1. Cowburn AS, Condliffe AM, Farahi N, Summers C, Chilvers ER. Advances in neutrophil biology: clinical implications. Chest. 2008;134(3):606–12. doi: 10.1378/chest.08-0422. 134/3/606 [pii]
    1. Le Cabec V, Cowland JB, Calafat J, Borregaard N. Targeting of proteins to granule subsets is determined by timing and not by sorting: The specific granule protein NGAL is localized to azurophil granules when expressed in HL-60 cells. Proc Natl Acad Sci U S A. 1996;93(13):6454–7.
    1. Brumell JH, Volchuk A, Sengelov H, Borregaard N, Cieutat AM, Bainton DF, Grinstein S, Klip A. Subcellular distribution of docking/fusion proteins in neutrophils, secretory cells with multiple exocytic compartments. J Immunol. 1995;155(12):5750–9.
    1. Borregaard N, Cowland JB. Granules of the human neutrophilic polymorphonuclear leukocyte. Blood. 1997;89(10):3503–21.
    1. DiStasi MR, Ley K. Opening the flood-gates: how neutrophil-endothelial interactions regulate permeability. Trends Immunol. 2009;30(11):547–56. doi: 10.1016/j.it.2009.07.012. S1471-4906(09)00157-4 [pii]
    1. Guzik K, Skret J, Smagur J, Bzowska M, Gajkowska B, Scott DA, Potempa JS. Cigarette smoke-exposed neutrophils die unconventionally but are rapidly phagocytosed by macrophages. Cell Death Dis. 2011;2:e131. doi: 10.1038/cddis.2011.13. cddis201113 [pii]
    1. Borregaard N. Development of neutrophil granule diversity. Ann N Y Acad Sci. 1997;832:62–8.
    1. Simon SI, Cherapanov V, Nadra I, Waddell TK, Seo SM, Wang Q, Doerschuk CM, Downey GP. Signaling functions of L-selectin in neutrophils: alterations in the cytoskeleton and colocalization with CD18. J Immunol. 1999;163(5):2891–901. ji_v163n5p2891 [pii]
    1. Kennedy AD, DeLeo FR. Neutrophil apoptosis and the resolution of infection. Immunol Res. 2009;43(1–3):25–61. doi: 10.1007/s12026-008-8049-6.
    1. Hayashi F, Means TK, Luster AD. Toll-like receptors stimulate human neutrophil function. Blood. 2003;102(7):2660–9. doi: 10.1182/blood-2003-04-1078. 2003-04-1078 [pii]
    1. Quinn MT, Ammons MC, Deleo FR. The expanding role of NADPH oxidases in health and disease: no longer just agents of death and destruction. Clin Sci (Lond) 2006;111(1):1–20. doi: 10.1042/CS20060059. CS20060059 [pii]
    1. Loesche WJ, Robinson JP, Flynn M, Hudson JL, Duque RE. Reduced oxidative function in gingival crevicular neutrophils in periodontal disease. Infect Immun. 1988;56(1):156–60.
    1. Reeves EP, Lu H, Jacobs HL, Messina CG, Bolsover S, Gabella G, Potma EO, Warley A, Roes J, Segal AW. Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature. 2002;416(6878):291–7. doi: 10.1038/416291a. 416291a [pii]
    1. Pham CT. Neutrophil serine proteases fine-tune the inflammatory response. Int J Biochem Cell Biol. 2008;40(6–7):1317–33. doi: 10.1016/j.biocel.2007.11.008. S1357-2725(07)00388-3 [pii]
    1. Almeida RP, Vanet A, Witko-Sarsat V, Melchior M, McCabe D, Gabay JE. Azurocidin, a natural antibiotic from human neutrophils: expression, antimicrobial activity, and secretion. Protein Expr Purif. 1996;7(4):355–66. doi: 10.1006/prep.1996.0053. S1046-5928(96)90053-4 [pii]
    1. Soehnlein O. Direct and alternative antimicrobial mechanisms of neutrophil-derived granule proteins. J Mol Med. 2009;87(12):1157–64. doi: 10.1007/s00109-009-0508-6.
    1. Chung WO, Dommisch H, Yin L, Dale BA. Expression of defensins in gingiva and their role in periodontal health and disease. Curr Pharm Des. 2007;13(30):3073–83.
    1. Ji S, Hyun J, Park E, Lee BL, Kim KK, Choi Y. Susceptibility of various oral bacteria to antimicrobial peptides and to phagocytosis by neutrophils. J Periodontal Res. 2007;42(5):410–9. doi: 10.1111/j.1600-0765.2006.00962.x. JRE962 [pii]
    1. de Haar SF, Hiemstra PS, van Steenbergen MT, Everts V, Beertsen W. Role of polymorphonuclear leukocyte-derived serine proteinases in defense against Actinobacillus actinomycetemcomitans. Infect Immun. 2006;74(9):5284–91. doi: 10.1128/IAI.02016-05. 74/9/5284 [pii]
    1. Permpanich P, Kowolik MJ, Galli DM. Resistance of fluorescent-labelled Actinobacillus actinomycetemcomitans strains to phagocytosis and killing by human neutrophils. Cell Microbiol. 2006;8(1):72–84. doi: 10.1111/j.1462-5822.2005.00601.x. CMI601 [pii]
    1. Havens AM, Chiu E, Taba M, Wang J, Shiozawa Y, Jung Y, Taichman LS, D’Silva NJ, Gopalakrishnan R, Wang C, Giannobile WV, Taichman RS. Stromal-derived factor-1alpha (CXCL12) levels increase in periodontal disease. J Periodontol. 2008;79(5):845–53. doi: 10.1902/jop.2008.070514.
    1. Page RC, Schroeder HE. Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest. 1976;34(3):235–49.
    1. Bainbridge B, Verma RK, Eastman C, Yehia B, Rivera M, Moffatt C, Bhattacharyya I, Lamont RJ, Kesavalu L. Role of Porphyromonas gingivalis phosphoserine phosphatase enzyme SerB in inflammation, immune response, and induction of alveolar bone resorption in rats. Infect Immun. 2010;78(11):4560–9. doi: 10.1128/IAI.00703-10. IAI.00703-10 [pii]
    1. Zaric S, Shelburne C, Darveau R, Quinn DJ, Weldon S, Taggart CC, Coulter WA. Impaired immune tolerance to Porphyromonas gingivalis lipopolysaccharide promotes neutrophil migration and decreased apoptosis. Infect Immun. 2010;78(10):4151–6. doi: 10.1128/IAI.00600-10. IAI.00600-10 [pii]
    1. Kachlany SC. Aggregatibacter actinomycetemcomitans leukotoxin: from threat to therapy. J Dent Res. 2010;89(6):561–70. doi: 10.1177/0022034510363682. 0022034510363682 [pii]
    1. Lally ET, Kieba IR, Sato A, Green CL, Rosenbloom J, Korostoff J, Wang JF, Shenker BJ, Ortlepp S, Robinson MK, Billings PC. RTX toxins recognize a beta2 integrin on the surface of human target cells. J Biol Chem. 1997;272(48):30463–9.
    1. Brinkmann V, Laube B, Abu Abed U, Goosmann C, Zychlinsky A. Neutrophil extracellular traps: how to generate and visualize them. J Vis Exp. 2010;(36) doi: 10.3791/1724. 1724 [pii]
    1. Logters T, Margraf S, Altrichter J, Cinatl J, Mitzner S, Windolf J, Scholz M. The clinical value of neutrophil extracellular traps. Med Microbiol Immunol. 2009;198(4):211–9. doi: 10.1007/s00430-009-0121-x.
    1. Krautgartner WD, Klappacher M, Hannig M, Obermayer A, Hartl D, Marcos V, Vitkov L. Fibrin mimics neutrophil extracellular traps in SEM. Ultrastruct Pathol. 2010;34(4):226–31. doi: 10.3109/01913121003725721.
    1. Vitkov L, Klappacher M, Hannig M, Krautgartner WD. Neutrophil fate in gingival crevicular fluid. Ultrastruct Pathol. 2010;34(1):25–30. doi: 10.3109/01913120903419989.
    1. Vitkov L, Klappacher M, Hannig M, Krautgartner WD. Extracellular neutrophil traps in periodontitis. J Periodontal Res. 2009;44(5):664–72. doi: 10.1111/j.1600-0765.2008.01175.x. JRE1175 [pii]
    1. Buchanan JT, Simpson AJ, Aziz RK, Liu GY, Kristian SA, Kotb M, Feramisco J, Nizet V. DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps. Curr Biol. 2006;16(4):396–400. doi: 10.1016/j.cub.2005.12.039. S0960-9822(06)01021-9 [pii]
    1. Potempa JG, Scott DA. Cigarette smoke-exposed neutrophils die unconventionally but are effectively phagocytosed. Cell Death and Disease. 2011 in press.
    1. Watson RW, Redmond HP, Wang JH, Condron C, Bouchier-Hayes D. Neutrophils undergo apoptosis following ingestion of Escherichia coli. J Immunol. 1996;156(10):3986–92.
    1. Cabrini M, Nahmod K, Geffner J. New insights into the mechanisms controlling neutrophil survival. Curr Opin Hematol. 2010;17(1):31–5. doi: 10.1097/MOH.0b013e3283333b29.
    1. Kobayashi SD, Voyich JM, Buhl CL, Stahl RM, DeLeo FR. Global changes in gene expression by human polymorphonuclear leukocytes during receptor-mediated phagocytosis: cell fate is regulated at the level of gene expression. Proc Natl Acad Sci U S A. 2002;99(10):6901–6. doi: 10.1073/pnas.092148299. 092148299 [pii]
    1. Kobayashi SD, Voyich JM, Whitney AR, DeLeo FR. Spontaneous neutrophil apoptosis and regulation of cell survival by granulocyte macrophage-colony stimulating factor. J Leukoc Biol. 2005;78(6):1408–18. doi: 10.1189/jlb.0605289. jlb.0605289 [pii]
    1. Huynh ML, Fadok VA, Henson PM. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J Clin Invest. 2002;109(1):41–50. doi: 10.1172/JCI11638.
    1. Jewett A, Hume WR, Le H, Huynh TN, Han YW, Cheng G, Shi W. Induction of apoptotic cell death in peripheral blood mononuclear and polymorphonuclear cells by an oral bacterium, Fusobacterium nucleatum. Infect Immun. 2000;68(4):1893–8.
    1. Ghosh A, Park JY, Fenno C, Kapila YL. Porphyromonas gingivalis, gamma interferon, and a proapoptotic fibronectin matrix form a synergistic trio that induces c-Jun N-terminal kinase 1-mediated nitric oxide generation and cell death. Infect Immun. 2008;76(12):5514–23. doi: 10.1128/IAI.00625-08. IAI.00625-08 [pii]
    1. Hotta K, Niwa M, Hara A, Ohno T, Wang X, Matsuno H, Kozawa O, Ito H, Kato K, Otsuka T, Matsui N, Uematsu T. The loss of susceptibility to apoptosis in exudated tissue neutrophils is associated with their nuclear factor-kappa B activation. Eur J Pharmacol. 2001;433(1):17–27. S0014-2999(01)01480-7 [pii]
    1. van Zandbergen G, Gieffers J, Kothe H, Rupp J, Bollinger A, Aga E, Klinger M, Brade H, Dalhoff K, Maass M, Solbach W, Laskay T. Chlamydia pneumoniae multiply in neutrophil granulocytes and delay their spontaneous apoptosis. J Immunol. 2004;172(3):1768–76.
    1. Johansson A, Claesson R, Hanstrom L, Sandstrom G, Kalfas S. Polymorphonuclear leukocyte degranulation induced by leukotoxin from Actinobacillus actinomycetemcomitans. J Periodontal Res. 2000;35(2):85–92.
    1. Taichman NS, Iwase M, Korchak H, Berthold P, Lally ET. Membranolytic activity of Actinobacillus actinomycetemcomitans leukotoxin. J Periodontal Res. 1991;26(3 Pt 2):258–60.
    1. Zysk G, Bejo L, Schneider-Wald BK, Nau R, Heinz H. Induction of necrosis and apoptosis of neutrophil granulocytes by Streptococcus pneumoniae. Clin Exp Immunol. 2000;122(1):61–6. cei1336 [pii]
    1. Hermant B, Bibert S, Concord E, Dublet B, Weidenhaupt M, Vernet T, Gulino-Debrac D. Identification of proteases involved in the proteolysis of vascular endothelium cadherin during neutrophil transmigration. J Biol Chem. 2003;278(16):14002–12. doi: 10.1074/jbc.M300351200. M300351200 [pii]
    1. Di Gennaro A, Kenne E, Wan M, Soehnlein O, Lindbom L, Haeggstrom JZ. Leukotriene B4-induced changes in vascular permeability are mediated by neutrophil release of heparin-binding protein (HBP/CAP37/azurocidin) FASEB J. 2009;23(6):1750–7. doi: 10.1096/fj.08-121277. fj.08-121277 [pii]
    1. Wedmore CV, Williams TJ. Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature. 1981;289(5799):646–50.
    1. Petrache I, Birukova A, Ramirez SI, Garcia JG, Verin AD. The role of the microtubules in tumor necrosis factor-alpha-induced endothelial cell permeability. Am J Respir Cell Mol Biol. 2003;28(5):574–81. doi: 10.1165/rcmb.2002-0075OC. 28/5/574 [pii]
    1. Strieter RM, Polverini PJ, Kunkel SL, Arenberg DA, Burdick MD, Kasper J, Dzuiba J, Van Damme J, Walz A, Marriott D, et al. The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem. 1995;270(45):27348–57.
    1. Lindbom L. Regulation of vascular permeability by neutrophils in acute inflammation. Chem Immunol Allergy. 2003;83:146–66.
    1. Nakatani K, Takeshita S, Tsujimoto H, Kawamura Y, Sekine I. Inhibitory effect of serine protease inhibitors on neutrophil-mediated endothelial cell injury. J Leukoc Biol. 2001;69(2):241–7.
    1. Hajishengallis G. Too old to fight? Aging and its toll on innate immunity. Mol Oral Microbiol. 2010;25(1):25–37. doi: 10.1111/j.2041-1014.2009.00562.x.
    1. Palmer RM, Wilson RF, Hasan AS, Scott DA. Mechanisms of action of environmental factors--tobacco smoking. J Clin Periodontol. 2005;32(Suppl 6):180–95.
    1. Johnstone AM, Koh A, Goldberg MB, Glogauer M. A hyperactive neutrophil phenotype in patients with refractory periodontitis. J Periodontol. 2007;78(9):1788–94. doi: 10.1902/jop.2007.070107.
    1. Matthews JB, Wright HJ, Roberts A, Cooper PR, Chapple IL. Hyperactivity and reactivity of peripheral blood neutrophils in chronic periodontitis. Clin Exp Immunol. 2007;147(2):255–64. doi: 10.1111/j.1365-2249.2006.03276.x. CEI3276 [pii]
    1. Zarbock A, Ley K. Mechanisms and consequences of neutrophil interaction with the endothelium. Am J Pathol. 2008;172(1):1–7. doi: 10.2353/ajpath.2008.070502. ajpath.2008.070502 [pii]
    1. Shapira L, Gordon B, Warbington M, Van Dyke TE. Priming effect of Porphyromonas gingivalis lipopolysaccharide on superoxide production by neutrophils from healthy and rapidly progressive periodontitis subjects. J Periodontol. 1994;65(2):129–33.
    1. Ashkenazi M, White RR, Dennison DK. Neutrophil modulation by Actinobacillus actinomycetemcomitans. II. Phagocytosis and development of respiratory burst. J Periodontal Res. 1992;27(5):457–65.
    1. Nicu EA, Van der Velden U, Everts V, Van Winkelhoff AJ, Roos D, Loos BG. Hyper-reactive PMNs in FcgammaRIIa 131 H/H genotype periodontitis patients. J Clin Periodontol. 2007;34(11):938–45. doi: 10.1111/j.1600-051X.2007.01136.x. CPE1136 [pii]
    1. Matthews JB, Wright HJ, Roberts A, Ling-Mountford N, Cooper PR, Chapple IL. Neutrophil hyper-responsiveness in periodontitis. J Dent Res. 2007;86(8):718–22. 86/8/718 [pii]
    1. Gustafsson A, Ito H, Asman B, Bergstrom K. Hyper-reactive mononuclear cells and neutrophils in chronic periodontitis. J Clin Periodontol. 2006;33(2):126–9. doi: 10.1111/j.1600-051X.2005.00883.x. CPE883 [pii]
    1. Restaino CG, Chaparro A, Valenzuela MA, Kettlun AM, Vernal R, Silva A, Puente J, Jaque MP, Leon R, Gamonal J. Stimulatory response of neutrophils from periodontitis patients with periodontal pathogens. Oral Dis. 2007;13(5):474–81. doi: 10.1111/j.1601-0825.2006.01323.x. ODI1323 [pii]
    1. Giannobile WV. Host-response therapeutics for periodontal diseases. J Periodontol. 2008;79(8 Suppl):1592–600. doi: 10.1902/jop.2008.080174.
    1. Opdenakker G, Van den Steen PE, Dubois B, Nelissen I, Van Coillie E, Masure S, Proost P, Van Damme J. Gelatinase B functions as regulator and effector in leukocyte biology. J Leukoc Biol. 2001;69(6):851–9.
    1. Holzhausen M, Cortelli JR, da Silva VA, Franco GC, Cortelli SC, Vergnolle N. Protease-activated receptor-2 (PAR(2)) in human periodontitis. J Dent Res. 2010;89(9):948–53. doi: 10.1177/0022034510373765. 0022034510373765 [pii]
    1. Ujiie Y, Oida S, Gomi K, Arai T, Fukae M. Neutrophil elastase is involved in the initial destruction of human periodontal ligament. J Periodontal Res. 2007;42(4):325–30. doi: 10.1111/j.1600-0765.2006.00952.x. JRE952 [pii]
    1. Lamster IB, Ahlo JK. Analysis of gingival crevicular fluid as applied to the diagnosis of oral and systemic diseases. Ann N Y Acad Sci. 2007;1098:216–29.
    1. Hanioka T, Matsuse R, Shigemoto Y, Ojima M, Shizukuishi S. Relationship between periodontal disease status and combination of biochemical assays of gingival crevicular fluid. J Periodontal Res. 2005;40(4):331–8. doi: 10.1111/j.1600-0765.2005.00807.x. JRE807 [pii]
    1. Figueredo CM, Fischer RG, Gustafsson A. Aberrant neutrophil reactions in periodontitis. J Periodontol. 2005;76(6):951–5. doi: 10.1902/jop.2005.76.6.951.
    1. Dommisch H, Vorderwulbecke S, Eberhard J, Steglich M, Jepsen S. SELDI-TOF-MS of gingival crevicular fluid--a methodological approach. Arch Oral Biol. 2009;54(9):803–9. doi: 10.1016/j.archoralbio.2009.05.011. S0003-9969(09)00148-4 [pii]
    1. Puklo M, Guentsch A, Hiemstra PS, Eick S, Potempa J. Analysis of neutrophil-derived antimicrobial peptides in gingival crevicular fluid suggests importance of cathelicidin LL-37 in the innate immune response against periodontogenic bacteria. Oral Microbiol Immunol. 2008;23(4):328–35. doi: 10.1111/j.1399-302X.2008.00433.x. OMI433 [pii]
    1. Dale BA, Kimball JR, Krisanaprakornkit S, Roberts F, Robinovitch M, O’Neal R, Valore EV, Ganz T, Anderson GM, Weinberg A. Localized antimicrobial peptide expression in human gingiva. J Periodontal Res. 2001;36(5):285–94.
    1. Kaner D, Bernimoulin JP, Kleber BM, Heizmann WR, Friedmann A. Gingival crevicular fluid levels of calprotectin and myeloperoxidase during therapy for generalized aggressive periodontitis. J Periodontal Res. 2006;41(2):132–9. doi: 10.1111/j.1600-0765.2005.00849.x. JRE849 [pii]
    1. Lorencini M, Silva JA, de la Hoz CL, Carvalho HF, Stach-Machado DR. Changes in MMPs and inflammatory cells in experimental gingivitis. Histol Histopathol. 2009;24(2):157–66.
    1. Tervahartiala T, Pirila E, Ceponis A, Maisi P, Salo T, Tuter G, Kallio P, Tornwall J, Srinivas R, Konttinen YT, Sorsa T. The in vivo expression of the collagenolytic matrix metalloproteinases (MMP-2, -8, -13, and -14) and matrilysin (MMP-7) in adult and localized juvenile periodontitis. J Dent Res. 2000;79(12):1969–77.
    1. Kubota T, Nomura T, Takahashi T, Hara K. Expression of mRNA for matrix metalloproteinases and tissue inhibitors of metalloproteinases in periodontitis-affected human gingival tissue. Arch Oral Biol. 1996;41(3):253–62. 0003-9969(95)00126-3 [pii]
    1. Xu L, Yu Z, Lee HM, Wolff MS, Golub LM, Sorsa T, Kuula H. Characteristics of collagenase-2 from gingival crevicular fluid and peri-implant sulcular fluid in periodontitis and peri-implantitis patients: pilot study. Acta Odontol Scand. 2008;66(4):219–24. doi: 10.1080/00016350802183393. 794876592 [pii]
    1. Emingil G, Kuula H, Sorsa T, Atilla G. Gingival crevicular fluid matrix metalloproteinase-25 and -26 levels in periodontal disease. J Periodontol. 2006;77(4):664–71. doi: 10.1902/jop.2006.050288.
    1. Smith PC, Munoz VC, Collados L, Oyarzun AD. In situ detection of matrix metalloproteinase-9 (MMP-9) in gingival epithelium in human periodontal disease. J Periodontal Res. 2004;39(2):87–92. 705 [pii]
    1. Guentsch A, Puklo M, Preshaw PM, Glockmann E, Pfister W, Potempa J, Eick S. Neutrophils in chronic and aggressive periodontitis in interaction with Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. J Periodontal Res. 2009;44(3):368–77. doi: 10.1111/j.1600-0765.2008.01113.x. JRE1113 [pii]
    1. Shin J, Ji S, Choi Y. Ability of oral bacteria to induce tissue-destructive molecules from human neutrophils. Oral Dis. 2008;14(4):327–34.
    1. Yamazaki T, Miyamoto M, Yamada S, Okuda K, Ishihara K. Surface protease of Treponema denticola hydrolyzes C3 and influences function of polymorphonuclear leukocytes. Microbes Infect. 2006;8(7):1758–63. doi: 10.1016/j.micinf.2006.02.013. S1286-4579(06)00120-1 [pii]
    1. Nemoto E, Kanaya S, Minamibuchi M, Shimauchi H. Cleavage of PDGF receptor on periodontal ligament cells by elastase. J Dent Res. 2005;84(7):629–33. 84/7/629 [pii]
    1. Dias IH, Matthews JB, Chapple IL, Wright HJ, Dunston CR, Griffiths HR. Activation of the neutrophil respiratory burst by plasma from periodontitis patients is mediated by pro-inflammatory cytokines. J Clin Periodontol. 2010 doi: 10.1111/j.1600-051X.2010.01628.x.
    1. Wright HJ, Chapple IL, Matthews JB, Cooper PR. Fusobacterium nucleatum regulation of neutrophil transcription. J Periodontal Res. 2010 doi: 10.1111/j.1600-0765.2010.01299.x. JRE1299 [pii]
    1. Dias IH, Marshall L, Lambert PA, Chapple IL, Matthews JB, Griffiths HR. Gingipains from Porphyromonas gingivalis increase the chemotactic and respiratory burst-priming properties of the 77-amino-acid interleukin-8 variant. Infect Immun. 2008;76(1):317–23. doi: 10.1128/IAI.00618-07. IAI.00618-07 [pii]
    1. Padrines M, Wolf M, Walz A, Baggiolini M. Interleukin-8 processing by neutrophil elastase, cathepsin G and proteinase-3. FEBS Lett. 1994;352(2):231–5. 0014-5793(94)00952-X [pii]
    1. Lim JK, Lu W, Hartley O, DeVico AL. N-terminal proteolytic processing by cathepsin G converts RANTES/CCL5 and related analogs into a truncated 4–68 variant. J Leukoc Biol. 2006;80(6):1395–404. doi: 10.1189/jlb.0406290. jlb.0406290 [pii]
    1. Coeshott C, Ohnemus C, Pilyavskaya A, Ross S, Wieczorek M, Kroona H, Leimer AH, Cheronis J. Converting enzyme-independent release of tumor necrosis factor alpha and IL-1beta from a stimulated human monocytic cell line in the presence of activated neutrophils or purified proteinase 3. Proc Natl Acad Sci U S A. 1999;96(11):6261–6.
    1. Bank U, Kupper B, Ansorge S. Inactivation of interleukin-6 by neutrophil proteases at sites of inflammation. Protective effects of soluble IL-6 receptor chains. Adv Exp Med Biol. 2000;477:431–7. doi: 10.1007/0-306-46826-3_43.
    1. Wittamer V, Bondue B, Guillabert A, Vassart G, Parmentier M, Communi D. Neutrophil-mediated maturation of chemerin: a link between innate and adaptive immunity. J Immunol. 2005;175(1):487–93. 175/1/487 [pii]
    1. Soehnlein O, Lindbom L. Neutrophil-derived azurocidin alarms the immune system. J Leukoc Biol. 2009;85(3):344–51. doi: 10.1189/jlb.0808495. jlb.0808495 [pii]
    1. Heissig B, Nishida C, Tashiro Y, Sato Y, Ishihara M, Ohki M, Gritli I, Rosenkvist J, Hattori K. Role of neutrophil-derived matrix metalloproteinase-9 in tissue regeneration. Histol Histopathol. 2010;25(6):765–70.
    1. Meyer-Hoffert U. Neutrophil-derived serine proteases modulate innate immune responses. Front Biosci. 2009;14:3409–18. 3462 [pii]
    1. Carlsson G, Wahlin YB, Johansson A, Olsson A, Eriksson T, Claesson R, Hanstrom L, Henter JI. Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia. J Periodontol. 2006;77(4):744–51. doi: 10.1902/jop.2006.050191.
    1. Putsep K, Carlsson G, Boman HG, Andersson M. Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet. 2002;360(9340):1144–9. doi: 10.1016/S0140-6736(02)11201-3. S0140-6736(02)11201-3 [pii]
    1. Spencer P, Fleming JE. Cyclic neutropenia: a literature review and report of case. ASDC J Dent Child. 1985;52(2):108–13.
    1. Hart TC, Atkinson JC. Mendelian forms of periodontitis. Periodontol 2000. 2007;45:95–112. doi: 10.1111/j.1600-0757.2007.00233.x. PRD233 [pii]
    1. Bailleul-Forestier I, Monod-Broca J, Benkerrou M, Mora F, Picard B. Generalized periodontitis associated with Chediak-Higashi syndrome. J Periodontol. 2008;79(7):1263–70. doi: 10.1902/jop.2008.070440.
    1. Shibutani T, Gen K, Shibata M, Horiguchi Y, Kondo N, Iwayama Y. Long-term follow-up of periodontitis in a patient with Chediak-Higashi syndrome. A case report. J Periodontol. 2000;71(6):1024–8. doi: 10.1902/jop.2000.71.6.1024.
    1. Khocht A, Viera-Negron YE, Ameri A, Abdelsayed R. Periodontitis associated with Chediak-Higashi syndrome in a young African American male. J Int Acad Periodontol. 2010;12(2):49–55.
    1. Wani AA, Devkar N, Patole MS, Shouche YS. Description of two new cathepsin C gene mutations in patients with Papillon-Lefevre syndrome. J Periodontol. 2006;77(2):233–7. doi: 10.1902/jop.2006.050124.
    1. Ullbro C, Twetman S. Review Paper: Dental treatment for patients with Papillon-Lefevre syndrome (PLS) Eur Arch Paediatr Dent. 2007;8(Suppl 1):4–11. 06.32 [pii]
    1. Cagli NA, Hakki SS, Dursun R, Toy H, Gokalp A, Ryu OH, Hart PS, Hart TC. Clinical, genetic, and biochemical findings in two siblings with Papillon-Lefevre Syndrome. J Periodontol. 2005;76(12):2322–9. doi: 10.1902/jop.2005.76.12.2322.
    1. Fokkema SJ, Timmerman MF, van der Weijden FA, Wolffe GN, Renggli HH. A possible association of alpha1-antitrypsin deficiency with the periodontal condition in adults. J Clin Periodontol. 1998;25(8):617–23.
    1. Peterson RJ, Marsh CL. The relationship of alpha1-antitrypsin to inflammatory periodontal disease. J Periodontol. 1979;50(1):31–5.
    1. Sandholm L, Saxen L. Concentrations of serum protease inhibitors and immunoglobulins in juvenile periodontitis. J Periodontal Res. 1983;18(5):527–33.
    1. Toomarian L, Hashemi N. Periodontal manifestation of leukocyte adhesion deficiency type I. Arch Iran Med. 2010;13(4):355–9. 0017 [pii] 010134/AIM.0017.
    1. Dababneh R, Al-Wahadneh AM, Hamadneh S, Khouri A, Bissada NF. Periodontal manifestation of leukocyte adhesion deficiency type I. J Periodontol. 2008;79(4):764–8. doi: 10.1902/jop.2008.070323.
    1. Parvaneh N, Mamishi S, Rezaei A, Rezaei N, Tamizifar B, Parvaneh L, Sherkat R, Ghalehbaghi B, Kashef S, Chavoshzadeh Z, Isaeian A, Ashrafi F, Aghamohammadi A. Characterization of 11 new cases of leukocyte adhesion deficiency type 1 with seven novel mutations in the ITGB2 gene. J Clin Immunol. 2010;30(5):756–60. doi: 10.1007/s10875-010-9433-2.
    1. Cox DP, Weathers DR. Leukocyte adhesion deficiency type 1: an important consideration in the clinical differential diagnosis of prepubertal periodontitis. A case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;105(1):86–90. doi: 10.1016/j.tripleo.2007.02.026. S1079-2104(07)00209-0 [pii]
    1. Giannopoulou C, Krause KH, Muller F. The NADPH oxidase NOX2 plays a role in periodontal pathologies. Semin Immunopathol. 2008;30(3):273–8. doi: 10.1007/s00281-008-0128-1.
    1. Dar-Odeh NS, Hayajneh WA, Abu-Hammad OA, Hammad HM, Al-Wahadneh AM, Bulos NK, Mahafzah AM, Shomaf MS, El-Maaytah MA, Bakri FG. Orofacial findings in chronic granulomatous disease: report of twelve patients and review of the literature. BMC Res Notes. 2010;3:37. doi: 10.1186/1756-0500-3-37. 1756-0500-3-37 [pii]
    1. Dimou NL, Nikolopoulos GK, Hamodrakas SJ, Bagos PG. Fcgamma receptor polymorphisms and their association with periodontal disease: a meta-analysis. J Clin Periodontol. 2010;37(3):255–65. doi: 10.1111/j.1600-051X.2009.01530.x. CPE1530 [pii]
    1. Ho YP, Yang YH, Ho KY, Wu YM, Tsai CC. The association of Fcgamma receptor IIIb genetic polymorphism and susceptibility to periodontitis in Taiwanese individuals. J Clin Periodontol. 2010;37(2):145–51. doi: 10.1111/j.1600-051X.2009.01507.x. CPE1507 [pii]
    1. Jones BE, Miettinen HM, Jesaitis AJ, Mills JS. Mutations of F110 and C126 of the formyl peptide receptor interfere with G-protein coupling and chemotaxis. J Periodontol. 2003;74(4):475–84. doi: 10.1902/jop.2003.74.4.475.
    1. Gwinn MR, Sharma A, De Nardin E. Single nucleotide polymorphisms of the N-formyl peptide receptor in localized juvenile periodontitis. J Periodontol. 1999;70(10):1194–201. doi: 10.1902/jop.1999.70.10.1194.
    1. Maney P, Walters JD. Formylpeptide receptor single nucleotide polymorphism 348T>C and its relationship to polymorphonuclear leukocyte chemotaxis in aggressive periodontitis. J Periodontol. 2009;80(9):1498–505. doi: 10.1902/jop.2009.090103.
    1. Maney P, Emecen P, Mills JS, Walters JD. Neutrophil formylpeptide receptor single nucleotide polymorphism 348T>C in aggressive periodontitis. J Periodontol. 2009;80(3):492–8. doi: 10.1902/jop.2009.080225.
    1. Gunji T, Onouchi Y, Nagasawa T, Katagiri S, Watanabe H, Kobayashi H, Arakawa S, Noguchi K, Hata A, Izumi Y, Ishikawa I. Functional polymorphisms of the FPR1 gene and aggressive periodontitis in Japanese. Biochem Biophys Res Commun. 2007;364(1):7–13. doi: 10.1016/j.bbrc.2007.09.105. S0006-291X(07)02078-5 [pii]
    1. Demmer RT, Papapanou PN. Epidemiologic patterns of chronic and aggressive periodontitis. Periodontol 2000. 2010;53:28–44. doi: 10.1111/j.1600-0757.2009.00326.x. PRD326 [pii]
    1. Ozturk A, Vieira AR. TLR4 as a risk factor for periodontal disease: a reappraisal. J Clin Periodontol. 2009;36(4):279–86. doi: 10.1111/j.1600-051X.2009.01370.x. CPE1370 [pii]
    1. Nikolopoulos GK, Dimou NL, Hamodrakas SJ, Bagos PG. Cytokine gene polymorphisms in periodontal disease: a meta-analysis of 53 studies including 4178 cases and 4590 controls. J Clin Periodontol. 2008;35(9):754–67. doi: 10.1111/j.1600-051X.2008.01298.x. CPE1298 [pii]
    1. Stein JM, Machulla HK, Smeets R, Lampert F, Reichert S. Human leukocyte antigen polymorphism in chronic and aggressive periodontitis among Caucasians: a meta-analysis. J Clin Periodontol. 2008;35(3):183–92. doi: 10.1111/j.1600-051X.2007.01189.x. CPE1189 [pii]
    1. Yoshie H, Kobayashi T, Tai H, Galicia JC. The role of genetic polymorphisms in periodontitis. Periodontol 2000. 2007;43:102–32. doi: 10.1111/j.1600-0757.2006.00164.x. PRD164 [pii]
    1. Saftig P, Beertsen W, Eskelinen EL. LAMP-2: a control step for phagosome and autophagosome maturation. Autophagy. 2008;4(4):510–2. 5724 [pii]
    1. Beertsen W, Willenborg M, Everts V, Zirogianni A, Podschun R, Schroder B, Eskelinen EL, Saftig P. Impaired phagosomal maturation in neutrophils leads to periodontitis in lysosomal-associated membrane protein-2 knockout mice. J Immunol. 2008;180(1):475–82. 180/1/475 [pii]
    1. Shiohara M, Gombart AF, Sekiguchi Y, Hidaka E, Ito S, Yamazaki T, Koeffler HP, Komiyama A. Phenotypic and functional alterations of peripheral blood monocytes in neutrophil-specific granule deficiency. J Leukoc Biol. 2004;75(2):190–7. doi: 10.1189/jlb.0203063. jlb.0203063 [pii]
    1. Nibali L, Parkar M, Brett P, Knight J, Tonetti MS, Griffiths GS. NADPH oxidase (CYBA) and FcgammaR polymorphisms as risk factors for aggressive periodontitis: a case-control association study. J Clin Periodontol. 2006;33(8):529–39. doi: 10.1111/j.1600-051X.2006.00952.x. CPE952 [pii]
    1. Dhanrajani PJ. Papillon-Lefevre syndrome: clinical presentation and a brief review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108(1):e1–7. doi: 10.1016/j.tripleo.2009.03.016. S1079-2104(09)00165-6 [pii]
    1. Fransson C, Berglundh T, Lindhe J. The effect of age on the development of gingivitis. Clinical, microbiological and histological findings. J Clin Periodontol. 1996;23(4):379–85.
    1. Siegel B, Weihe E, Bette M, Nusing RM, Flores-de-Jacoby L, Mengel R. The effect of age on prostaglandin-synthesizing enzymes in the development of gingivitis. J Periodontal Res. 2007;42(3):259–66. doi: 10.1111/j.1600-0765.2006.00942.x. JRE942 [pii]
    1. Butcher S, Chahel H, Lord JM. Review article: ageing and the neutrophil: no appetite for killing? Immunology. 2000;100(4):411–6. imm079 [pii]
    1. Gomez CR, Nomellini V, Faunce DE, Kovacs EJ. Innate immunity and aging. Exp Gerontol. 2008;43(8):718–28. doi: 10.1016/j.exger.2008.05.016. S0531-5565(08)00163-0 [pii]
    1. Guntsch A, Erler M, Preshaw PM, Sigusch BW, Klinger G, Glockmann E. Effect of smoking on crevicular polymorphonuclear neutrophil function in periodontally healthy subjects. J Periodontal Res. 2006;41(3):184–8. doi: 10.1111/j.1600-0765.2005.00852.x. JRE852 [pii]
    1. Morozumi T, Kubota T, Sugita N, Itagaki M, Yoshie H. Alterations of gene expression in human neutrophils induced by smoking cessation. J Clin Periodontol. 2004;31(12):1110–6. doi: 10.1111/j.1600-051X.2004.00612.x. CPE612 [pii]
    1. Scott DA, Bagaitkar J. Smoking and innate immune (dys)function. In: Bernhard D, editor. Cigarette Smoke Toxicity. Linking Individual Chemicals to Human Diseases. Wiley-VCH Verlag GmbH & Co. KGaA; Weinheim, Germany: 2011.
    1. Terashima T, Klut ME, English D, Hards J, Hogg JC, van Eeden SF. Cigarette smoking causes sequestration of polymorphonuclear leukocytes released from the bone marrow in lung microvessels. Am J Respir Cell Mol Biol. 1999;20(1):171–7.
    1. Xu M, Scott JE, Liu KZ, Bishop HR, Renaud DE, Palmer RM, Soussi-Gounni A, Scott DA. The influence of nicotine on granulocytic differentiation - inhibition of the oxidative burst and bacterial killing and increased matrix metalloproteinase-9 release. BMC Cell Biol. 2008;9(1):19.
    1. Pitzer JE, Del Zoppo GJ, Schmid-Schonbein GW. Neutrophil activation in smokers. Biorheology. 1996;33(1):45–58.
    1. Selby C, Drost E, Brown D, Howie S, MacNee W. Inhibition of neutrophil adherence and movement by acute cigarette smoke exposure. Experimental Lung Research. 1992;18(6):813–27.
    1. Hind CR, Joyce H, Tennent GA, Pepys MB, Pride NB. Plasma leucocyte elastase concentrations in smokers. Journal of Clinical Pathology. 1991;44(3):232–5.
    1. Seow WK, Thong YH, Nelson RD, MacFarlane GD, Herzberg MC. Nicotine-induced release of elastase and eicosanoids by human neutrophils. Inflammation. 1994;18(2):119–27.
    1. Nakamura T, Ebihara I, Shimada N, Koide H. Effect of cigarette smoking on plasma metalloproteinase-9 concentration. Clinica Chimica Acta. 1998;276(2):173–7. S0009-8981(98)00104-1 [pii]
    1. Liu KZ, Hynes A, Man A, Alsagheer A, Singer DL, Scott DA. Increased local matrix metalloproteinase-8 expression in the periodontal connective tissues of smokers with periodontal disease. Biochim Biophys Acta. 2006;1762(8):775–80.
    1. Guzik K, Skret J, Smagur J, Bzowska M, Gajkowska B, Scott DA, Potempa JS. Cigarette smoke-exposed neutrophils die unconventionally but are rapidly phagocytosed by macrophages. Cell Death and Disease. 2011 in press.
    1. Zappacosta B, Persichilli S, Minucci A, Stasio ED, Carlino P, Pagliari G, Giardina B, Sole PD. Effect of aqueous cigarette smoke extract on the chemiluminescence kinetics of polymorphonuclear leukocytes and on their glycolytic and phagocytic activity. Luminescence. 2001;16(5):315–9.
    1. Benhammou K, Lee M, Strook M, Sullivan B, Logel J, Raschen K, Gotti C, Leonard S. [(3)H]Nicotine binding in peripheral blood cells of smokers is correlated with the number of cigarettes smoked per day. Neuropharmacology. 2000;39(13):2818–29. S0028390800001532 [pii]
    1. Lee HY, Kehrli ME, Jr, Brogden KA, Gallup JM, Ackermann MR. Influence of beta(2)-integrin adhesion molecule expression and pulmonary infection with Pasteurella haemolytica on cytokine gene expression in cattle. Infection & Immunity. 2000;68(7):4274–81.
    1. Fredriksson M, Bergstrom K, Asman B. IL-8 and TNF-alpha from peripheral neutrophils and acute-phase proteins in periodontitis. Journal of Clinical Periodontology. 2002;29(2):123–8. cpe290206 [pii]
    1. Zeilhofer HU, Schorr W. Role of interleukin-8 in neutrophil signaling. Current Opinion in Hematology. 2000;7(3):178–82.
    1. Scott DA, Stapleton JA, Wilson RF, Sutherland G, Palmer RM, Coward PY, Gustavsson G. Dramatic decline in circulating intercellular adhesion molecule-1 concentration on quitting tobacco smoking. Blood Cells Mol Dis. 2000;26(3):255–8.
    1. Scott DATD, Wilson RF, Coward PY, Odell EW, Poston RN, Matthews JP, Palmer RM. The acute influence of tobacco smoking on adhesion molecule expression on monocytes and neutrophils and on circulating adhesion molecule levels in vivo. Addiction Biology. 2000;5:195–205.
    1. Rehani K, Scott DA, Renaud D, Hamza H, Williams LR, Wang H, Martin M. Cotinine-induced convergence of the cholinergic and PI3 kinase-dependent anti-inflammatory pathways in innate immune cells. Biochim Biophys Acta. 2008;1783(3):375–82.
    1. Ulloa L, Tracey KJ. The “cytokine profile”: a code for sepsis. Trends Mol Med. 2005;11(2):56–63.
    1. Huston JM, Tracey KJ. The pulse of inflammation: heart rate variability, the cholinergic anti-inflammatory pathway and implications for therapy. J Intern Med. 2011;269(1):45–53. doi: 10.1111/j.1365-2796.2010.02321.x.
    1. Su X, Matthay MA, Malik AB. Requisite role of the cholinergic alpha7 nicotinic acetylcholine receptor pathway in suppressing Gram-negative sepsis-induced acute lung inflammatory injury. Journal of Immunology. 2010;184(1):401–10. doi: 10.4049/jimmunol.0901808. jimmunol.0901808 [pii]
    1. Huston JM, Rosas-Ballina M, Xue X, Dowling O, Ochani K, Ochani M, Yeboah MM, Chatterjee PK, Tracey KJ, Metz CN. Cholinergic neural signals to the spleen down-regulate leukocyte trafficking via CD11b. Journal of Immunology. 2009;183(1):552–9. doi: 10.4049/jimmunol.0802684. 183/1/552 [pii]
    1. Sadis C, Teske G, Stokman G, Kubjak C, Claessen N, Moore F, Loi P, Diallo B, Barvais L, Goldman M, Florquin S, Le Moine A. Nicotine protects kidney from renal ischemia/reperfusion injury through the cholinergic anti-inflammatory pathway. PLoS One. 2007;2(5):e469. doi: 10.1371/journal.pone.0000469.
    1. Giebelen IA, van Westerloo DJ, LaRosa GJ, de Vos AF, van der Poll T. Stimulation of alpha 7 cholinergic receptors inhibits lipopolysaccharide-induced neutrophil recruitment by a tumor necrosis factor alpha-independent mechanism. Shock. 2007;27(4):443–7. doi: 10.1097/. 00024382-200704000-00017 [pii]
    1. van Westerloo DJ, Giebelen IA, Florquin S, Daalhuisen J, Bruno MJ, de Vos AF, Tracey KJ, van der Poll T. The cholinergic anti-inflammatory pathway regulates the host response during septic peritonitis. Journal of Infectious Diseases. 2005;191(12):2138–48. doi: 10.1086/430323. JID33743 [pii]
    1. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000;405(6785):458–62.
    1. Huston JM, Ochani M, Rosas-Ballina M, Liao H, Ochani K, Pavlov VA, Gallowitsch-Puerta M, Ashok M, Czura CJ, Foxwell B, Tracey KJ, Ulloa L. Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis. J Exp Med. 2006;203(7):1623–8.
    1. Rosas-Ballina M, Goldstein RS, Gallowitsch-Puerta M, Yang L, Valdes-Ferrer SI, Patel NB, Chavan S, Al-Abed Y, Yang H, Tracey KJ. The selective alpha7 agonist GTS-21 attenuates cytokine production in human whole blood and human monocytes activated by ligands for TLR2, TLR3, TLR4, TLR9, and RAGE. Mol Med. 2009;15(7–8):195–202.
    1. van Westerloo DJ, Giebelen IA, Florquin S, Bruno MJ, Larosa GJ, Ulloa L, Tracey KJ, van der Poll T. The vagus nerve and nicotinic receptors modulate experimental pancreatitis severity in mice. Gastroenterology. 2006;130(6):1822–30.
    1. Scott DA, Martin M. Exploitation of the nicotinic anti-inflammatory pathway for the treatment of epithelial inflammatory diseases. World J Gastroenterol. 2006;12(46):7451–9.
    1. Pavlov VA, Ochani M, Yang LH, Gallowitsch-Puerta M, Ochani K, Lin X, Levi J, Parrish WR, Rosas-Ballina M, Czura CJ, Larosa GJ, Miller EJ, Tracey KJ, Al-Abed Y. Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis. Crit Care Med. 2007;35(4):1139–44.
    1. Matsunaga K, Klein TW, Friedman H, Yamamoto Y. Involvement of nicotinic acetylcholine receptors in suppression of antimicrobial activity and cytokine responses of alveolar macrophages to Legionella pneumophila infection by nicotine. J Immunol. 2001;167(11):6518–24.
    1. de Heens GL, Kikkert R, Aarden LA, van der Velden U, Loos BG. Effects of smoking on the ex vivo cytokine production in periodontitis. J Periodontal Res. 2009;44(1):28–34.
    1. Rehani K, Wang H, Garcia CA, Kinane DF, Martin M. Toll-like receptor-mediated production of IL-1Ra is negatively regulated by GSK3 via the MAPK ERK1/2. J Immunol. 2009;182(1):547–53.
    1. Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature. 2003;421(6921):384–8.
    1. Pabst MJ, Pabst KM, Collier JA, Coleman TC, Lemons-Prince ML, Godat MS, Waring MB, Babu JP. Inhibition of neutrophil and monocyte defensive functions by nicotine. J Periodontol. 1995;66(12):1047–55.
    1. Murphy EA, Danna-Lopes D, Sarfati I, Rao SK, Cohen JR. Nicotine-stimulated elastase activity release by neutrophils in patients with abdominal aortic aneurysms. Annals of Vascular Surgery. 1998;12(1):41–5.
    1. Cheng SL, Wang HC, Yu CJ, Tsao PN, Carmeliet P, Cheng SJ, Yang PC. Prevention of elastase-induced emphysema in placenta growth factor knock-out mice. Respir Res. 2009;10:115. doi: 10.1186/1465-9921-10-115. 1465-9921-10-115 [pii]
    1. Preshaw PM. Host response modulation in periodontics. Periodontol 2000. 2008;48:92–110. doi: 10.1111/j.1600-0757.2008.00252.x. PRD252 [pii]
    1. Klein C. Congenital neutropenia. Hematology Am Soc Hematol Educ Program. 2009:344–50. doi: 10.1182/asheducation-2009.1.344. 2009/1/344 [pii]
    1. Matarasso S, Daniele V, Iorio Siciliano V, Mignogna MD, Andreuccetti G, Cafiero C. The effect of recombinant granulocyte colony-stimulating factor on oral and periodontal manifestations in a patient with cyclic neutropenia: a case report. Int J Dent. 2009;2009:654239. doi: 10.1155/2009/654239.
    1. Burgos RA, Hidalgo MA, Figueroa CD, Conejeros I, Hancke JL. New potential targets to modulate neutrophil function in inflammation. Mini Rev Med Chem. 2009;9(2):153–68.

Source: PubMed

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