HUMAN EOSINOPHILS CONSTITUTIVELY EXPRESS A FUNCTIONAL INTERLEUKIN-4 RECEPTOR - INTERLEUKIN-4-INDUCED PRIMING OF CHEMOTACTIC RESPONSES AND INDUCTION OF PI-3 KINASE-ACTIVITY

Similar to interleukin-3 (IL-3), IL-5, and granulocyte macrophage colo ny-stimulating factor (GM-CSF), IL-4 can be secreted by several cell t ypes involved in allergic inflammatory reactions, and therefore can af fect eosinophil function similarly. In this study, we investigated the presence of an IL-4 receptor (IL-4R) on human eosinophils. When two d ifferent monoclonal antibodies (mAbs) against the IL-4R alpha-chain (I L-4R) were used, fluorescent-activate cell sorter analysis revealed th e presence of an IL-4R alpha on both eosinophils of normal donors and atopic dermatitis patients. In addition, the expression of the IL-2R g amma-chain, a functional component of the IL-4R in some cell types, wa s demonstrated. The IL-4Ra appeared to be expressed constitutively, an d stimulation with cytokines IL-2, IL-3, IL-5, GM-CSF, and interferon- gamma did not further increase IL-4R alpha expression. Evidence for an IL-4R alpha was further substantiated by mRNA analysis. Both Northern blot analysis and reverse transcriptase/polymerase chain reaction rev ealed the presence of mRNA for the IL-4R alpha in eosinophils from nor mal individuals and AD patients. Furthermore, we demonstrated that bot h IL-4 and IL-13 were capable of inducing PI-3 kinase activity in huma n eosinophils. Because this activation could be inhibited by an IL-4R alpha mAb, we conclude that both cytokines can activate human eosinoph ils through binding to a receptor complex comprising the IL-4R alpha a nd-yet to be identified-associated proteins. In addition, the involvem ent of IL-4 in functional responses was studied. IL-4 appeared to ''pr ime'' eosinophils to respond chemotactically toward regulated on activ ation, normal T cells expressed and secreted, but did not affect plate let-activating factor-induced chemotaxis. Taken together, these data s how the presence of a functional IL-4R on human eosinophils.