Functional regulation of beta 1 integrins on human eosinophils by divalent cations and cytokines.
Divalent cations and various soluble stimuli can alter cell adherence by affecting the avidity of adhesion molecules. We hypothesized that beta 1 integrin function of human eosinophils may be altered by divalent cations and eosinophil-activating cytokines such as interleukin-5 (IL-5). Expression of the beta 1 integrin activation epitope recognized by monoclonal antibody (mAb) 15/7 was evaluated by flow cytometry using purified eosinophils from allergic subjects, normal subjects, and late-phase bronchoalveolar lavage (BAL) fluids. Rapid and reversible 15/7 binding on eosinophils from each source was induced in Mn2+ (0.01-1 mM) but not in buffers containing other divalent cations and occurred without affecting the total level of beta 1 integrin expression (quantified using mAb 33B6). Augmentation of eosinophil adhesion to immobilized vascular cell adhesion molecule (VCAM-1) in Mn2+ followed a similar concentration dependence as mAb 15/7 binding. Net binding to VCAM-1 in Mn2+ was completely inhibited with a mixture of alpha 4 and beta 1 integrin mAb while beta 2 integrin mAb had no effect. Exposure of eosinophils from allergic subjects to as little as 1 pg/ml IL-5 completely inhibited mAb 15/7 binding induced by Mn2+. In contrast, increased binding of mAb 15/7 in Mn2+ was not blocked by IL-5 in eosinophils from normal subjects. For eosinophils from allergic subjects, IL-5 also inhibited Mn(2+)-induced adhesion to VCAM-1. Thus, beta 1 integrins on eosinophils from allergic and nonallergic subjects are modulated differently by Mn2+ and IL-5. Altered beta 1 integrin avidity may be one mechanism involved in preferential eosinophil recruitment in vivo.
Department of Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224-6801, USA.
S J
SJ
Werfel
T A
TA
Yednock
K
K
Matsumoto
S A
SA
Sterbinsky
R P
RP
Schleimer
B S
BS
Bochner
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001249:Asthma / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002413:Cations, Divalent; D002448:Cell Adhesion / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology*; D004804:Eosinophils / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D006967:Hypersensitivity / Q000097:blood; D019012:Integrin beta1 / Q000276:immunology / Q000502:physiology*; D015848:Interleukin-5 / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology*; D012220:Rhinitis / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000911:Antibodies, Monoclonal; D002413:Cations, Divalent; D016207:Cytokines; D019012:Integrin beta1; D015848:Interleukin-5; D019010:Vascular Cell Adhesion Molecule-1; D008345:Manganese