Integrin activation States and eosinophil recruitment in asthma

Mats W Johansson, Deane F Mosher, Mats W Johansson, Deane F Mosher

Abstract

Eosinophil arrest and recruitment to the airway in asthma are mediated, at least in part, by integrins. Eosinophils express α4β1, α6β1, αLβ2, αMβ2, αXβ2, αDβ2, and α4β7 integrins, which interact with counter-receptors on other cells or ligands in the extracellular matrix. Whether a given integrin-ligand pair mediates cell adhesion and migration depends on the activation state of the integrin. Integrins exist in an inactive bent, an intermediate-activity extended closed, and a high-activity extended open conformation. Integrin activation states can be monitored by conformation-specific monoclonal antibodies (mAbs). Studies in mice indicate that both β1 and β2 integrins mediate eosinophil recruitment to the lung. In vitro studies indicate that α4β1 and αMβ2 are the principal integrins mediating eosinophil adhesion, including to vascular cell adhesion molecule-1 and the novel αMβ2 ligand periostin. In vivo, blood eosinophils have intermediate-activity β1 integrins, as judged by mAb N29, apparently resulting from eosinophil binding of P-selectin on the surface of activated platelets, and have a proportion of their β2 integrins in the intermediate conformation, as judged by mAb KIM-127, apparently due to exposure to low concentrations of interleukin-5 (IL-5). Airway eosinophils recovered by bronchoalveolar lavage (BAL) after segmental antigen challenge have high-activity β1 integrins and high-activity αMβ2 that does not require IL-5. Here we review information on how the activation states of eosinophil β1 and β2 integrins correlate with measurements of eosinophil recruitment and pulmonary function in asthma. Blood eosinophil N29 reactivity is associated with decreased lung function under various circumstances in non-severe asthma and KIM-127 with BAL eosinophil numbers, indicating that intermediate-activity α4β1 and αMβ2 of blood eosinophils are important for eosinophil arrest and consequently for recruitment and aspects of asthma.

Keywords: adhesion; asthma; eosinophils; inflammation; integrins.

Figures

Figure 1
Figure 1
Models of integrin conformations with epitopes for activation-sensitive mAbs. (A) Domains of an integrin α subunit. (B) Domains of an integrin β subunit. (C) Conformational changes during activation of αMβ2 that uncover epitopes for anti-β2 KIM-127 and mAb24, and anti-αM CBRM1/5. (D) Conformational changes during activation of α4β1 that uncover epitopes for anti-β1 N29, 8E3, HUTS-21, and 9EG7. (1) Inactive, bent conformations; (2) intermediate-activity, extended, closed conformations; (3) high-activity, extended, open conformations. In (C) conformation 1 of αMβ2 is presumably KIM-127−/mAb24−/CBRM1/5−, conformation 2 KIM-127+/mAb24−/CBRM1/5−, and conformation 3 KIM-127+/mAb24+/CBRM1/5+. In (D) conformation 1 of α4β1 is presumably N29−/8E3−/HUTS-21−/9EG7−, conformation 2 N29+/8E3+/HUTS-21−/9EG7−, and conformation 3 N29+/8E3+/HUTS-21+/9EG7+. Green circle, ligand-binding site in αI domain in (C) or βI domain in (D), or binding site in βI domain for activated αI domain in (C). Green arrow, cytoplasmic proteins, including talin and kindlins, that bind the β integrin subunit tail and mediate activation. β-prop., β-propeller domain; EGF, integrin epidermal growth factor-like domain; PSI, plexin-semaphorin-integrin domain. Based on (Luo and Springer, ; Luo et al., ; Barthel et al., ; Evans et al., ; Hogg et al., 2011).

References

    1. Agache I., Akdis C., Jutel M., Virchow J. C. (2012). Untangling asthma phenotypes and endotypes. Allergy 67, 835–84610.1111/j.1398-9995.2012.02832.x
    1. Alon R., Dustin M. L. (2007). Force as a facilitator of integrin conformational changes during leukocyte arrest on blood vessels and antigen-presenting cells. Immunity 26, 17–2710.1016/j.immuni.2007.01.002
    1. Anderson G. P. (2008). Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet 372, 1107–111910.1016/S0140-6736(08)61018-1
    1. Askari J. A., Buckley P. A., Mould A. P., Humphries M. J. (2009). Linking integrin conformation to function. J. Cell Sci. 122, 165–17010.1242/jcs.018556
    1. Banerjee E. R., Jiang Y., Henderson W. R., Jr., Latchman Y., Papayannopoulou T. (2009). Absence of alpha 4 but not beta 2 integrins restrains development of chronic allergic asthma using mouse genetic models. Exp. Hematol. 37, 715–72710.1016/j.exphem.2009.03.010
    1. Banerjee E. R., Jiang Y., Henderson W. R., Jr., Scott L. M., Papayannopoulou T. (2007). Alpha4 and beta2 integrins have nonredundant roles for asthma development, but for optimal allergen sensitization only alpha4 is critical. Exp. Hematol. 35, 605–61710.1016/j.exphem.2007.01.052
    1. Barthel S. R., Annis D. S., Mosher D. F., Johansson M. W. (2006a). Differential engagement of modules 1 and 4 of vascular cell adhesion molecule-1 (CD106) by integrins alpha4beta1 (CD49d/29) and alphaMbeta2 (CD11b/18) of eosinophils. J. Biol. Chem. 281, 32175–3218710.1074/jbc.M600943200
    1. Barthel S. R., Jarjour N. N., Mosher D. F., Johansson M. W. (2006b). Dissection of the hyperadhesive phenotype of airway eosinophils in asthma. Am. J. Respir. Cell Mol. Biol. 35, 378–38610.1165/rcmb.2006-0027OC
    1. Barthel S. R., Johansson M. W., McNamee D. M., Mosher D. F. (2008). Roles of integrin activation in eosinophil function and the eosinophilic inflammation of asthma. J. Leukoc. Biol. 83, 1–1210.1189/jlb.0607344
    1. Bazzoni G., Shih D. T., Buck C. A., Hemler M. E. (1995). Monoclonal antibody 9EG7 defines a novel beta 1 integrin epitope induced by soluble ligand and manganese, but inhibited by calcium. J. Biol. Chem. 270, 25570–2557710.1074/jbc.270.43.25570
    1. Beglova N., Blacklow S. C., Takagi J., Springer T. A. (2002). Cysteine-rich module structure reveals a fulcrum for integrin rearrangement upon activation. Nat. Struct. Biol. 9, 282–28710.1038/nsb779
    1. Bentley J. K., Linn M. J., Lei J., Comstock A., Zhao Y., Hershenson M. B. (2012). Periostin knockout mice are protected from house dust mite allergen-induced lung inflammation [abstract]. Am. J. Respir. Crit. Care Med. 185, A6873
    1. Blanchard C., Mingler M. K., McBride M., Putnam P. E., Collins M. H., Chang G., et al. (2008). Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses. Mucosal Immunol. 1, 289–29610.1038/mi.2008.15
    1. Blanchard C., Rothenberg M. E. (2009). Biology of the eosinophil. Adv. Immunol. 101, 81–12110.1016/S0065-2776(08)01003-1
    1. Busse W. W., Lemanske R. F., Jr. (2001). Asthma. N. Engl. J. Med. 344, 350–36210.1056/NEJM200102013440507
    1. Busse W. W., Ring J., Huss-Marp J., Kahn J. E. (2010). A review of treatment with mepolizumab, an anti-IL-5 mAb, in hypereosinophilic syndromes and asthma. J. Allergy Clin. Immunol. 125, 803–81310.1016/j.jaci.2010.04.005
    1. Byron A., Humphries J. D., Askari J. A., Craig S. E., Mould A. P., Humphries M. J. (2009). Anti-integrin monoclonal antibodies. J. Cell Sci. 122, 4009–401110.1242/jcs.056770
    1. Coe A. P., Askari J. A., Kline A. D., Robinson M. K., Kirby H., Stephens P. E., et al. (2001). Generation of a minimal alpha5beta1 integrin-Fc fragment. J. Biol. Chem. 276, 35854–3586610.1074/jbc.M103639200
    1. Dransfield I., Hogg N. (1989). Regulated expression of Mg2+ binding epitope on leukocyte integrin alpha subunits. EMBO J. 8, 3759–3765
    1. Evans D. J., Barnes P. J., Spaethe S. M., van Alstyne E. L., Mitchell M. I., O’Connor B. J. (1996). Effect of a leukotriene B4 receptor antagonist, LY293111, on allergen induced responses in asthma. Thorax 51, 1178–118410.1136/thx.51.12.1248
    1. Evans R., Patzak I., Svensson L., De Filippo K., Jones K., McDowall A., et al. (2009). Integrins in immunity. J. Cell Sci. 122, 215–22510.1242/jcs.019117
    1. Flood-Page P., Menzies-Gow A., Phipps S., Ying S., Wangoo A., Ludwig M. S., et al. (2003). Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. J. Clin. Invest. 112, 1029–103610.1172/JCI200317974
    1. Gauvreau G. M., Evans M. Y. (2007). Allergen inhalation challenge: a human model of asthma exacerbation. Contrib. Microbiol. 14, 21–3210.1159/000107052
    1. Haldar P., Brightling C. E., Hargadon B., Gupta S., Monteiro W., Sousa A., et al. (2009). Mepolizumab and exacerbations of refractory eosinophilic asthma. N. Engl. J. Med. 360, 973–98410.1056/NEJMoa0808991
    1. Haldar P., Pavord I. D., Shaw D. E., Berry M. A., Thomas M., Brightling C. E., et al. (2008). Cluster analysis and clinical asthma phenotypes. Am. J. Respir. Crit. Care Med. 178, 218–22410.1164/rccm.200711-1754OC
    1. Harburger D. S., Calderwood D. A. (2009). Integrin signalling at a glance. J. Cell Sci. 122, 159–16310.1242/jcs.052910
    1. Hastie A. T., Moore W. C., Meyers D. A., Vestal P. L., Li H., Peters S. P., et al. (2010). Analyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes. J. Allergy Clin. Immunol. 125, 1028–103610.1016/j.jaci.2010.02.008
    1. Hayashi N., Yoshimoto T., Izuhara K., Matsui K., Tanaka T., Nakanishi K. (2007). T helper 1 cells stimulated with ovalbumin and IL-18 induce airway hyperresponsiveness and lung fibrosis by IFN-gamma and IL-13 production. Proc. Natl. Acad. Sci. U.S.A. 104, 14765–1477010.1073/pnas.0706378104
    1. Hogan S. P., Rosenberg H. F., Moqbel R., Phipps S., Foster P. S., Lacy P., et al. (2008). Eosinophils: biological properties and role in health and disease. Clin. Exp. Allergy 38, 709–75010.1111/j.1365-2222.2008.02958.x
    1. Hogg N., Patzak I., Willenbrock F. (2011). The insider’s guide to leukocyte integrin signalling and function. Nat. Rev. Immunol. 11, 416–42610.1038/nri2986
    1. Humphries J. D., Byron A., Humphries M. J. (2006). Integrin ligands at a glance. J. Cell Sci. 119, 3901–390310.1242/jcs.03098
    1. Humphries M. J. (2004). Monoclonal antibodies as probes of integrin priming and activation. Biochem. Soc. Trans. 32, 407–41110.1042/BST0320407
    1. Huttenlocher A., Ginsberg M. H., Horwitz A. F. (1996). Modulation of cell migration by integrin-mediated cytoskeletal linkages and ligand-binding affinity. J. Cell Biol. 134, 1551–156210.1083/jcb.134.6.1551
    1. Hynes R. O. (1987). Integrins: a family of cell surface receptors. Cell 48, 549–55410.1016/0092-8674(87)90704-5
    1. Jarjour N. N., Calhoun W. J., Kelly E. A., Gleich G. J., Schwartz L. B., Busse W. W. (1997). The immediate and late allergic response to segmental bronchopulmonary provocation in asthma. Am. J. Respir. Crit. Care Med. 155, 1515–1521
    1. Johansson M. W., Barthel S. R., Swenson C. A., Evans M. D., Jarjour N. N., Mosher D. F., et al. (2006). Eosinophil beta(1) integrin activation state correlates with asthma activity in a blind study of inhaled corticosteroid withdrawal. J. Allergy Clin. Immunol. 117, 1502–150410.1016/j.jaci.2006.02.032
    1. Johansson M. W., Gunderson K. A., Kelly E. A. B., Denlinger L. C., Jarjour N. N., Mosher D. F. (2013a). Anti-IL-5 attenuates activation and surface density of β2-integrins on circulating eosinophils after segmental antigen challenge. Clin. Exp. Allergy 43, 292–30310.1111/j.1365-2222.2012.04065.x
    1. Johansson M. W., Annis D. S., Mosher D. F. (2013b). AlphaMbeta2 integrin-mediated adhesion and motility of interleukin-5-stimulated eosinophils on periostin. Am. J. Respir. Cell Mol. Biol. (in press) Available from: as 10.1165/rcmb.2012-0150OC
    1. Johansson M. W., Han S. T., Gunderson K. A., Busse W. W., Jarjour N. N., Mosher D. F. (2012). Platelet activation, P-selectin, and eosinophil beta1-integrin activation in asthma. Am. J. Respir. Crit. Care Med. 185, 498–50710.1164/rccm.201109-1712OC
    1. Johansson M. W., Han S.-T., Gunderson K. A., Montgomery R. R., Busse W. W., Jarjour N. N., et al. (2011). Platelet activation, P-selectin mobilization, and eosinophil beta1 integrin activation occur in asthma and are associated with clinical phenotypes [abstract]. Am. J. Respir. Crit. Care Med. 183, A4335
    1. Johansson M. W., Kelly E. A., Busse W. W., Jarjour N. N., Mosher D. F. (2008). Up-regulation and activation of eosinophil integrins in blood and airway after segmental lung antigen challenge. J. Immunol. 180, 7622–7635
    1. Johansson M. W., Lye M. H., Barthel S. R., Duffy A. K., Annis D. S., Mosher D. F. (2004). Eosinophils adhere to vascular cell adhesion molecule-1 via podosomes. Am. J. Respir. Cell Mol. Biol. 31, 413–42210.1165/rcmb.2004-0099OC
    1. Johansson M. W., Mosher D. F. (2011). Activation of {beta}1 integrins on blood eosinophils by P-selectin. Am. J. Respir. Cell Mol. Biol. 45, 889–89710.1165/rcmb.2010-0402OC
    1. Johnsson M., Bove M., Bergquist H., Olsson M., Fornwall S., Hassel K., et al. (2011). Distinctive blood eosinophilic phenotypes and cytokine patterns in eosinophilic esophagitis, inflammatory bowel disease and airway allergy. J. Innate Immun. 3, 594–60410.1159/000331326
    1. Joseph J., Benedict S., Safa W., Joseph M. (2004). Serum interleukin-5 levels are elevated in mild and moderate persistent asthma irrespective of regular inhaled glucocorticoid therapy. BMC Pulm. Med. 4:2.10.1186/1471-2466-4-2
    1. Kay A. B., Phipps S., Robinson D. S. (2004). A role for eosinophils in airway remodelling in asthma. Trends Immunol. 25, 477–48210.1016/j.it.2004.07.006
    1. Kelly E. A. B., Busse W. W., Jarjour N. N. (2003). A comparison of the airway response to segmental antigen bronchoprovocation in atopic asthma and allergic rhinitis. J. Allergy Clin. Immunol. 111, 79–8610.1016/S0091-6749(03)81221-6
    1. Kita H. (2011). Eosinophils: multifaceted biological properties and roles in health and disease. Immunol. Rev. 242, 161–17710.1111/j.1600-065X.2011.01026.x
    1. Koenderman L., van der Bruggen T., Schweizer R. C., Warringa R. A., Coffer P., Caldenhoven E., et al. (1996). Eosinophil priming by cytokines: from cellular signal to in vivo modulation. Eur. Respir. J. Suppl. 22, 119s–125s
    1. Lee J. J., Jacobsen E. A., McGarry M. P., Schleimer R. P., Lee N. A. (2010). Eosinophils in health and disease: the LIAR hypothesis. Clin. Exp. Allergy 40, 563–57510.1111/j.1365-2222.2010.03484.x
    1. Leitinger B., Hogg N. (2000). Effects of I domain deletion on the function of the beta2 integrin lymphocyte function-associated antigen-1. Mol. Biol. Cell 11, 677–690
    1. Lenter M., Uhlig H., Hamann A., Jeno P., Imhof B., Vestweber D. (1993). A monoclonal antibody against an activation epitope on mouse integrin chain beta 1 blocks adhesion of lymphocytes to the endothelial integrin alpha 6 beta 1. Proc. Natl. Acad. Sci. U.S.A. 90, 9051–905510.1073/pnas.90.19.9051
    1. Lotvall J., Akdis C. A., Bacharier L. B., Bjermer L., Casale T. B., Custovic A., et al. (2011). Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J. Allergy Clin. Immunol. 127, 355–36010.1016/j.jaci.2010.11.037
    1. Lu C., Shimaoka M., Zang Q., Takagi J., Springer T. A. (2001). Locking in alternate conformations of the integrin alphaLbeta2 I domain with disulfide bonds reveals functional relationships among integrin domains. Proc. Natl. Acad. Sci. U.S.A. 98, 2393–239810.1073/pnas.161272798
    1. Luo B. H., Carman C. V., Springer T. A. (2007). Structural basis of integrin regulation and signaling. Annu. Rev. Immunol. 25, 619–64710.1146/annurev.immunol.25.022106.141618
    1. Luo B. H., Springer T. A. (2006). Integrin structures and conformational signaling. Curr. Opin. Cell Biol. 18, 579–58610.1016/j.ceb.2006.08.005
    1. Luque A., Gomez M., Puzon W., Takada Y., Sanchez-Madrid F., Cabanas C. (1996). Activated conformations of very late activation integrins detected by a group of antibodies (HUTS) specific for a novel regulatory region (355-425) of the common beta 1 chain. J. Biol. Chem. 271, 11067–1107510.1074/jbc.271.19.11067
    1. Margadant C., Monsuur H. N., Norman J. C., Sonnenberg A. (2011). Mechanisms of integrin activation and trafficking. Curr. Opin. Cell Biol. 23, 607–61410.1016/j.ceb.2011.08.005
    1. Mastalerz L., Sanak M., Szczeklik A. (2001). Serum interleukin-5 in aspirin-induced asthma. Clin. Exp. Allergy 31, 1036–104010.1046/j.1365-2222.2001.01105.x
    1. Masuoka M., Shiraishi H., Ohta S., Suzuki S., Arima K., Aoki S., et al. (2012). Periostin promotes chronic allergic inflammation in response to Th2 cytokines. J. Clin. Invest. 122, 2590–260010.1172/JCI58978
    1. Moore W. C., Meyers D. A., Wenzel S. E., Teague W. G., Li H., Li X., et al. (2010). Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am. J. Respir. Crit. Care Med. 181, 315–32310.1164/rccm.201003-0321UP
    1. Mould A. P., Travis M. A., Barton S. J., Hamilton J. A., Askari J. A., Craig S. E., et al. (2005). Evidence that monoclonal antibodies directed against the integrin beta subunit plexin/semaphorin/integrin domain stimulate function by inducing receptor extension. J. Biol. Chem. 280, 4238–424610.1074/jbc.M412240200
    1. Nair P., Pizzichini M. M., Kjarsgaard M., Inman M. D., Efthimiadis A., Pizzichini E., et al. (2009). Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N. Engl. J. Med. 360, 985–99310.1056/NEJMoa0805435
    1. Ni H., Li A., Simonsen N., Wilkins J. A. (1998). Integrin activation by dithiothreitol or Mn2+ induces a ligand-occupied conformation and exposure of a novel NH2-terminal regulatory site on the beta1 integrin chain. J. Biol. Chem. 273, 7981–798710.1074/jbc.273.38.24797
    1. Oxvig C., Lu C., Springer T. A. (1999). Conformational changes in tertiary structure near the ligand binding site of an integrin I domain. Proc. Natl. Acad. Sci. U.S.A. 96, 2215–222010.1073/pnas.96.5.2215
    1. Palecek S. P., Loftus J. C., Ginsberg M. H., Lauffenburger D. A., Horwitz A. F. (1997). Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. Nature 385, 537–54010.1038/385537a0
    1. Pavord I. D., Korn S., Howarth P., Bleecker E. R., Buhl R., Keene O. N., et al. (2012). Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 380, 651–65910.1016/S0140-6736(12)60988-X
    1. Pitchford S. C., Momi S., Giannini S., Casali L., Spina D., Page C. P., et al. (2005). Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation. Blood 105, 2074–208110.1182/blood-2004-06-2282
    1. Ramos-Barbon D., Fraga-Iriso R., Brienza N. S., Montero-Martinez C., Verea-Hernando H., Olivenstein R., et al. (2010). T Cells localize with proliferating smooth muscle alpha-actin+ cell compartments in asthma. Am. J. Respir. Crit. Care Med. 182, 317–32410.1164/rccm.200905-0745OC
    1. Rennard S. I., Basset G., Lecossier D., O’Donnell K. M., Pinkston P., Martin P. G., et al. (1986). Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. J. Appl. Physiol. 60, 532–538
    1. Robinson D. S. (2013). Mepolizumab treatment for asthma. Expert Opin. Biol. Ther. 13, 295–30210.1517/14712598.2012.725717
    1. Robinson M. K., Andrew D., Rosen H., Brown D., Ortlepp S., Stephens P., et al. (1992). Antibody against the Leu-CAM beta-chain (CD18) promotes both LFA-1- and CR3-dependent adhesion events. J. Immunol. 148, 1080–1085
    1. Rosenberg H. F., Dyer K. D., Foster P. S. (2013). Eosinophils: changing perspectives in health and disease. Nat. Rev. Immunol. 13, 9–2210.1038/nri3341
    1. Rosenberg H. F., Phipps S., Foster P. S. (2007). Eosinophil trafficking in allergy and asthma. J. Allergy Clin. Immunol. 119, 1303–131010.1016/j.jaci.2007.03.048
    1. Ruoslahti E. (1991). Integrins. J. Clin. Invest. 87, 1–510.1172/JCI114957
    1. Schleimer R. P., Sterbinsky S. A., Kaiser J., Bickel C. A., Klunk D. A., Tomioka K., et al. (1992). IL 4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium. Association with expression of VCAM-1. J. Immunol. 148, 1086–1092
    1. Scott K. A., Wardlaw A. J. (2006). Eosinophilic airway disorders. Semin. Respir. Crit. Care Med. 27, 128–13310.1055/s-2006-939515
    1. Shattil S. J., Kim C., Ginsberg M. H. (2010). The final steps of integrin activation: the end game. Nat. Rev. Mol. Cell Biol. 11, 288–30010.1038/nrm2871
    1. Simpson J. L., Scott R., Boyle M. J., Gibson P. G. (2006). Inflammatory subtypes in asthma: assessment and identification using induced sputum. Respirology 11, 54–6110.1111/j.1440-1843.2006.00784.x
    1. Siroux V., Basagana X., Boudier A., Pin I., Garcia-Aymerich J., Vesin A., et al. (2011). Identifying adult asthma phenotypes using a clustering approach. Eur. Respir. J. 38, 310–31710.1183/09031936.00120810
    1. Springer T. A. (1994). Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76, 301–31410.1016/0092-8674(94)90337-9
    1. Symon F. A., Lawrence M. B., Williamson M. L., Walsh G. M., Watson S. R., Wardlaw A. J. (1996). Functional and structural characterization of the eosinophil P-selectin ligand. J. Immunol. 157, 1711–1719
    1. Takayama G., Arima K., Kanaji T., Toda S., Tanaka H., Shoji S., et al. (2006). Periostin: a novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals. J. Allergy Clin. Immunol. 118, 98–10410.1016/j.jaci.2006.02.046
    1. Teran L. M., Carroll M. P., Shute J. K., Holgate S. T. (1999). Interleukin 5 release into asthmatic airways 4 and 24 hours after endobronchial allergen challenge: its relationship with eosinophil recruitment. Cytokine 11, 518–52210.1006/cyto.1998.0457
    1. Walsh G. M., Mermod J. J., Hartnell A., Kay A. B., Wardlaw A. J. (1991). Human eosinophil, but not neutrophil, adherence to IL-1-stimulated human umbilical vascular endothelial cells is alpha 4 beta 1 (very late antigen-4) dependent. J. Immunol. 146, 3419–3423
    1. Wang F., He X. Y., Baines K. J., Gunawardhana L. P., Simpson J. L., Li F., et al. (2011). Different inflammatory phenotypes in adults and children with acute asthma. Eur. Respir. J. 38, 567–57410.1183/09031936.00170110
    1. Weller P. F., Rand T. H., Goelz S. E., Chi-Rosso G., Lobb R. R. (1991). Human eosinophil adherence to vascular endothelium mediated by binding to vascular cell adhesion molecule 1 and endothelial leukocyte adhesion molecule 1. Proc. Natl. Acad. Sci. U.S.A. 88, 7430–743310.1073/pnas.88.16.7430
    1. Wenzel S. E. (2012). Asthma phenotypes: the evolution from clinical to molecular approaches. Nat. Med. 18, 716–72510.1038/nm.2678
    1. Wilkins J. A., Li A., Ni H., Stupack D. G., Shen C. (1996). Control of beta1 integrin function. Localization of stimulatory epitopes. J. Biol. Chem. 271, 3046–305110.1074/jbc.271.6.3255
    1. Wills-Karp M., Karp C. L. (2004). Eosinophils in asthma: remodeling a tangled tale. Science 305, 1726–172910.1126/science.1104134
    1. Woodruff P. G., Boushey H. A., Dolganov G. M., Barker C. S., Yang Y. H., Donnelly S., et al. (2007). Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids. Proc. Natl. Acad. Sci. U.S.A. 104, 15858–1586310.1073/pnas.0707413104
    1. Woodruff P. G., Modrek B., Choy D. F., Jia G., Abbas A. R., Ellwanger A., et al. (2009). T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am. J. Respir. Crit. Care Med. 180, 388–39510.1164/rccm.200903-0392OC
    1. Woolley K. L., Adelroth E., Woolley M. J., Ellis R., Jordana M., O’Byrne P. M. (1995). Effects of allergen challenge on eosinophils, eosinophil cationic protein, and granulocyte macrophage colony-stimulating factor in mild asthma. Am. J. Respir. Crit. Care Med. 151, 1915–1924
    1. Yuyama N., Davies D. E., Akaiwa M., Matsui K., Hamasaki Y., Suminami Y., et al. (2002). Analysis of novel disease-related genes in bronchial asthma. Cytokine 19, 287–29610.1006/cyto.2002.1972
    1. Zhu X., Munoz N. M., Kim K. P., Sano H., Cho W., Leff A. R. (1999). Cytosolic phospholipase A2 activation is essential for beta 1 and beta 2 integrin-dependent adhesion of human eosinophils. J. Immunol. 163, 3423–3429

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