Am. J. Respir. Cell Mol. Biol., Volume 19, Number 4, October, 1998 691-699

Human Eosinophils Constitutively Express a Functional Interleukin-4 Receptor: Interleukin-4 -Induced Priming of Chemotactic Responses and Induction of PI-3 Kinase Activity

Gerald R. Dubois, René C. Schweizer, Coraline Versluis, Carla A. F. M. Bruijnzeel-Koomen, and Piet L. B. Bruijnzeel

Departments of Dermatology/Allergology and Pulmonary Diseases, University Hospital Utrecht, Utrecht; and Department of Pharmacology, TNO-Pharma, Rijswijk, The Netherlands

Similar to interleukin-3 (IL-3), IL-5, and granulocyte macrophage colony-stimulating factor (GM-CSF), IL-4 can be secreted by several cell types involved in allergic inflammatory reactions, and therefore can affect eosinophil function similarly. In this study, we investigated the presence of an IL-4 receptor (IL-4R) on human eosinophils. When two different monoclonal antibodies (mAbs) against the IL-4R -chain (IL-4R) were used, fluorescent-activated cell sorter analysis revealed the presence of an IL-4R on both eosinophils of normal donors and atopic dermatitis patients. In addition, the expression of the IL-2R -chain, a functional component of the IL-4R in some cell types, was demonstrated. The IL-4R appeared to be expressed constitutively, and stimulation with cytokines IL-2, IL-3, IL-5, GM-CSF, and interferon- did not further increase IL-4R expression. Evidence for an IL-4R was further substantiated by mRNA analysis. Both Northern blot analysis and reverse transcriptase/polymerase chain reaction revealed the presence of mRNA for the IL-4R in eosinophils from normal individuals and AD patients. Furthermore, we demonstrated that both IL-4 and IL-13 were capable of inducing PI-3 kinase activity in human eosinophils. Because this activation could be inhibited by an IL-4R mAb, we conclude that both cytokines can activate human eosinophils through binding to a receptor complex comprising the IL-4R andyet to be identifiedassociated proteins. In addition, the involvement of IL-4 in functional responses was studied. IL-4 appeared to "prime" eosinophils to respond chemotactically toward regulated on activation, normal T cells expressed and secreted, but did not affect platelet-activating factor-induced chemotaxis. Taken together, these data show the presence of a functional IL-4R on human eosinophils.

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