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Anti‐ IL ‐5 attenuates activation and surface density of β 2 ‐integrins on circulating eosinophils after segmental antigen challenge
Author(s) -
Johansson M. W.,
Gunderson K. A.,
Kelly E. A. B.,
Denlinger L. C.,
Jarjour N. N.,
Mosher D. F.
Publication year - 2013
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2012.04065.x
Subject(s) - eosinophil , integrin , immunology , bronchoalveolar lavage , antigen , eosinophil cationic protein , monoclonal antibody , chemistry , antibody , receptor , biology , medicine , asthma , lung , biochemistry
Summary Background IL ‐5 activates α M β 2 integrin on blood eosinophils in vitro . Eosinophils in bronchoalveolar lavage ( BAL ) following segmental antigen challenge have activated β 2 ‐integrins. Objective To identify roles for IL‐5 in regulating human eosinophil integrins in vivo . Methods Blood and BAL eosinophils were analysed by flow cytometry in ten subjects with allergic asthma who underwent a segmental antigen challenge protocol before and after anti‐ IL ‐5 administration. Results Blood eosinophil reactivity with monoclonal antibody (mAb) KIM ‐127, which recognizes partially activated β 2 ‐integrins, was decreased after anti‐ IL ‐5. Before anti‐ IL ‐5, surface densities of blood eosinophil β 2 , α M and α L integrin subunits increased modestly post challenge. After anti‐ IL ‐5, such increases did not occur. Before or after anti‐ IL ‐5, surface densities of β 2 , α M , α L and α D and reactivity with KIM ‐127 and mAb CBRM 1/5, which recognizes high‐activity α M β 2 , were similarly high on BAL eosinophils 48 h post‐challenge. Density and activation state of β 1 ‐integrins on blood and BAL eosinophils were not impacted by anti‐ IL ‐5, even though anti‐ IL ‐5 ablated a modest post‐challenge increase on blood or BAL eosinophils of P‐selectin glycoprotein ligand‐1 ( PSGL ‐1), a receptor for P‐selectin that causes activation of β 1 ‐integrins. Forward scatter of blood eosinophils post‐challenge was less heterogeneous and on the average decreased after anti‐ IL ‐5; however, anti‐ IL ‐5 had no effect on the decreased forward scatter of eosinophils in post‐challenge BAL compared with eosinophils in blood. Blood eosinophil KIM ‐127 reactivity at the time of challenge correlated with the percentage of eosinophils in BAL post‐challenge. Conclusion and Clinical Relevance IL ‐5 supports a heterogeneous population of circulating eosinophils with partially activated β 2 ‐integrins and is responsible for up‐regulation of β 2 ‐integrins and PSGL ‐1 on circulating eosinophils following segmental antigen challenge but has minimal effects on properties of eosinophils in BAL . Dampening of β 2 ‐integrin function of eosinophils in transit to inflamed airway may contribute to the decrease in lung inflammation caused by anti‐ IL ‐5.