A CRUCIAL ROLE FOR BETA-2 INTEGRIN IN THE ACTIVATION OF EOSINOPHILS STIMULATED BY IGG

An IgG-coated surface, such as found on parasites, is one of the most effective physiologic stimuli for eosinophil activation. Recent eviden ce suggests that cellular adhesion, especially that through the beta 2 integrin, is an important step in cellular activation and accumulatio n. Therefore, we investigated the role of adhesion molecules in IgG-st imulated eosinophil functions. Cross-linking of eosinophil cytophilic IgG by anti-IgG immobilized to tissue culture plates induced degranula tion, whereas soluble anti-IgG did not. Similarly, eosinophils exposed to human IgG immobilized to plates adhered and degranulated; in addit ion, adherence and subsequent degranulation were inhibited by mAbs to CD18 and CD11b, but not by mAb to CD29, suggesting an important role o f beta 2 integrin for these responses. Eosinophil degranulation induce d by IgG covalently coupled to Sepharose 4B beads was also inhibited b y mAb to CD18. Furthermore, fibrinogen, a ligand for CD11b/18, showed synergistic enhancement of IgG-induced degranulation when it was co-im mobilized with IgG to plates. A morphologic study showed that eosinoph ils, stimulated by immobilized IgG, protrude numerous pseudopods; this morphologic change was inhibited by mAb to CD18. This cellular adhesi on seems to affect the early signaling events in eosinophils because t he production of inositol phosphates was abolished by mAb to CD18. Int erestingly, although superoxide production by eosinophils triggered by immobilized IgG was inhibited by mAb to CD18, superoxide production a nd morphologic change of neutrophils were not. These results suggest t hat cell adhesion through CD11b/18 is a crucial step for the activatio n, signaling, and effector function of eosinophils stimulated by IgG.