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 b eta 1 integrin function of human eosinophils may be altered by divalen t cations and eosinophil-activating cytokines such as interleukin-5 (I L-5). Expression of the beta 1 integrin activation epitope recognized by monoclonal antibody (mAb) 15/7 was evaluated by flow cytometry usin g purified eosinophils from allergic subjects, normal subjects, and la te-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 (quant ified using mAb 33B6). Augmentation of eosinophil adhesion to immobili zed vascular cell adhesion molecule (VCAM-1) in Mn2+ followed a simila r 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 eosi nophils from allergic subjects to as little as 1 pg/ml IL-5 completely inhibited mAb 15/7 binding induced by Mn2+. In contrast, increased bi nding 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 inh ibited Mn2+-induced adhesion to VCAM-1. Thus, beta 1 integrins on eosi nophils from allergic and nonallergic subjects are modulated different ly by Mn2+ and IL-5. Altered beta 1 integrin avidity may be one mechan ism involved in preferential eosinophil recruitment in vivo.