Human eosinophils constitutively express a functional interleukin-4 receptor: Interleukin-4-induced priming of chemotactic responses and induction of PI-3 kinase activity
Human eosinophils constitutively express a functional interleukin-4 receptor: Interleukin-4-induced priming of chemotactic responses and induction of PI-3 kinase activity
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DOI：
10.1165/ajrcmb.19.4.3208
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发表时间：
1998-10-01
影响因子：
6.4
通讯作者：
Bruijnzeel, PLB
中科院分区：
文献类型：
--
作者：
Dubois, GR;Schweizer, RC;Bruijnzeel, PLB
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) 类似，IL-4 可由参与过敏性炎症反应的几种细胞类型分泌，因此可以类似地影响嗜酸性粒细胞功能。在这项研究中，我们研究了人嗜酸性粒细胞上是否存在 IL-4 受体 (IL-4R)。当使用两种不同的针对 IL-4R α 链 (IL-4R) 的单克隆抗体 (mAb) 时，荧光激活细胞分选仪分析显示正常供体和特应性皮炎患者的嗜酸性粒细胞上都存在 IL-4R α。此外，还证明了 IL-2R γ 链（IL-4R 的功能成分）在某些细胞类型中的表达。 IL-4Ra 似乎是组成型表达，并且用细胞因子 IL-2、IL-3、IL-5、GM-CSF 和干扰素-γ 刺激不会进一步增加 IL-4R α 表达。 IL-4R α 的证据通过 mRNA 分析得到进一步证实。 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 患者的嗜酸性粒细胞中存在 IL-4R α mRNA。此外，我们证明 IL-4 和 IL-13 都能够诱导人嗜酸性粒细胞中的 PI-3 激酶活性。由于这种激活可以被 IL-4R α mAb 抑制，因此我们得出结论，两种细胞因子都可以通过与包含 IL-4R α 和尚未鉴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 在功能反应中的参与。 IL-4似乎“引发”嗜酸性粒细胞对激活、表达和分泌的正常T细胞的调节作出趋化反应，但不影响血小板激活因子诱导的趋化性。总而言之，这些数据表明人嗜酸性粒细胞上存在功能性 IL-4R。
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.