Human eosinophils constitutively express a functional interleukin-4 receptor: interleukin-4 -induced priming of chemotactic responses and induction of PI-3 kinase activity

G R Dubois, R C Schweizer, C Versluis, C A Bruijnzeel-Koomen, P L Bruijnzeel

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 alpha-chain (IL-4Ralpha) were used, fluorescent-activated cell sorter analysis revealed the presence of an IL-4Ralpha on both eosinophils of normal donors and atopic dermatitis patients. In addition, the expression of the IL-2R gamma-chain, a functional component of the IL-4R in some cell types, was demonstrated. The IL-4Ralpha appeared to be expressed constitutively, and stimulation with cytokines IL-2, IL-3, IL-5, GM-CSF, and interferon-gamma did not further increase IL-4Ralpha expression. Evidence for an IL-4Ralpha was further substantiated by mRNA analysis. Both Northern blot analysis and reverse transcriptase/polymerase chain reaction revealed the presence of mRNA for the IL-4Ralpha 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-4Ralpha mAb, we conclude that both cytokines can activate human eosinophils through binding to a receptor complex comprising the IL-4Ralpha and-yet to be identified-associated 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.

Original languageEnglish
Pages (from-to)691-9
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume19
Issue number4
DOIs
Publication statusPublished - 1998

Keywords

  • Antibodies, Monoclonal
  • Blotting, Northern
  • Chemokine CCL5
  • Chemotaxis
  • Dermatitis, Atopic
  • Enzyme Activation
  • Eosinophils
  • Flow Cytometry
  • Gene Expression
  • Humans
  • Interleukin-13
  • Interleukin-4
  • Lymphoma, B-Cell
  • Phosphatidylinositol 3-Kinases
  • RNA, Messenger
  • Receptors, Interleukin-4
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes
  • Tumor Cells, Cultured

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