Dubois G R, Schweizer R C, Versluis C, Bruijnzeel-Koomen C A, Bruijnzeel P L
Departments of Dermatology/Allergology and Pulmonary Diseases, University Hospital Utrecht, The Netherlands.
Am J Respir Cell Mol Biol. 1998 Oct;19(4):691-9. doi: 10.1165/ajrcmb.19.4.3208.
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.
与白细胞介素-3（IL-3）、IL-5和粒细胞巨噬细胞集落刺激因子（GM-CSF）相似，IL-4可由参与过敏性炎症反应的多种细胞类型分泌，因此可同样影响嗜酸性粒细胞的功能。在本研究中，我们调查了人嗜酸性粒细胞上IL-4受体（IL-4R）的存在情况。当使用两种针对IL-4Rα链（IL-4Rα）的不同单克隆抗体（mAb）时，荧光激活细胞分选分析显示正常供体和特应性皮炎患者的嗜酸性粒细胞上均存在IL-4Rα。此外，还证实了IL-2Rγ链的表达，它是某些细胞类型中IL-4R的功能成分。IL-4Rα似乎是组成性表达的，用细胞因子IL-2、IL-3、IL-5、GM-CSF和干扰素-γ刺激并未进一步增加IL-4Rα的表达。mRNA分析进一步证实了IL-4Rα的存在。Northern印迹分析和逆转录酶/聚合酶链反应均显示正常个体和AD患者嗜酸性粒细胞中存在IL-4Rα的mRNA。此外，我们证明IL-4和IL-13均能够诱导人嗜酸性粒细胞中的PI-3激酶活性。由于这种激活可被IL-4Rα mAb抑制，我们得出结论，这两种细胞因子均可通过与包含IL-4Rα和尚未确定的相关蛋白的受体复合物结合来激活人嗜酸性粒细胞。此外，还研究了IL-4在功能反应中的作用。IL-4似乎可“启动”嗜酸性粒细胞对活化正常T细胞表达和分泌的调节因子产生趋化反应，但不影响血小板活化因子诱导的趋化作用。综上所述，这些数据表明人嗜酸性粒细胞上存在功能性IL-4R。
