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

被引:42
作者
Dubois, GR
Schweizer, RC
Versluis, C
Bruijnzeel-Koomen, CAFM
Bruijnzeel, PLB
机构
[1] Univ Utrecht Hosp, Dept Dermatol Allergol, Utrecht, Netherlands
[2] Univ Utrecht Hosp, Dept Pulm Dis, Utrecht, Netherlands
[3] TNO, Dept Pharmacol, NL-2280 AA Rijswijk, Netherlands
关键词
D O I
10.1165/ajrcmb.19.4.3208
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-4R) were used, fluorescent-activate cell sorter analysis revealed the presence of an IL-4R alpha 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-4Ra 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-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 revealed the presence of mRNA for the IL-4R alpha 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 alpha mAb, we conclude that both cytokines can activate human eosinophils through binding to a receptor complex comprising the IL-4R alpha 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.
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收藏
页码:691 / 699
页数:9
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