Am. J. Respir. Cell Mol. Biol., Vol 14, No. 1, 01 1996, 44-52.
Functional regulation of beta 1 integrins on human eosinophils by divalent cations and cytokines
SJ Werfel, TA Yednock, K Matsumoto, SA Sterbinsky, RP Schleimer and BS Bochner
Department of Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224- 6801, USA.
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.
