Human peripheral blood basophils primed by interleukin 3 (IL-3) produce IL-4 in response to immunoglobulin E receptor stimulation.
Human peripheral blood basophils primed by interleukin 3 (IL-3) produce IL-4 in response to immunoglobulin E receptor stimulation.
复制标题
白介素3（IL-3）引发的人外周血嗜碱性嗜碱性粒细胞对免疫球蛋白E受体刺激产生IL-4。
DOI：
10.1084/jem.177.3.605
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发表时间：
1993-03-01
期刊：
影响因子：
--
通讯作者：
Dahinden CA
中科院分区：
文献类型：
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作者：
Brunner T;Heusser CH;Dahinden CA
与大多数细胞因子相反，白细胞介素 4 (IL-4) 的表达仅限于 T 淋巴细胞，肥大细胞系和肥大细胞除外，正如最近在啮齿动物中所证实的那样。然而，人们对人类非淋巴细胞产生 IL-4 的能力知之甚少。在这项研究中，我们证明成熟的人类嗜碱性粒细胞能够表达 IL-4，并与脂质介质白三烯 C4 相比检查 IL-4 产生的调节。 IL-4 是在用 IL-3 培养的嗜碱性粒细胞的免疫球蛋白 E 受体 (IgER) 激活后产生的，IL-3 是一种细胞因子，之前已证明可以增强这些细胞释放炎症介质的能力。在一些实验中，单独激活 IL-3 或 IgER 也能诱导 IL-4 的产生接近检测限。 IL-3 对 IgER 依赖性 IL-4 表达的影响是剂量和时间依赖性的：最大 IL-4 产生发生在嗜碱性粒细胞预暴露于 3-10 ng/ml IL-3 的 18 至 48 小时之间。 IgER 诱导的 IL-4 合成以及与 IL-3 一起培养的嗜碱性粒细胞的释放在 6 小时后快速且完整。与 IL-3 不同，其他细胞因子（IL-5、粒细胞/巨噬细胞集落刺激因子和神经生长因子）也能促进嗜碱性粒细胞增强组胺和白三烯 C4 的释放，但不会促进 IgER 诱导的 IL-4 合成。嗜碱性粒细胞似乎分泌“TH2 样”细胞因子谱，因为 IgER 激活时没有产生可检测的 IL-2 或干扰素 γ。平行培养的单核细胞（耗尽嗜碱性粒细胞）不会响应 IL-3 和/或 IgER 激活而释放 IL-4，并且在佛波酯和钙离子载体非特异性激活时产生的 IL-4 比嗜碱性粒细胞少约十倍。因此，人嗜碱性粒细胞是 IL-4 的重要细胞来源，因此除了其炎症效应功能外，还可能调节 T 辅助细胞和 B 细胞的分化，特别是在过敏性疾病中。
In contrast to most cytokines, interleukin 4 (IL-4) expression is restricted to T lymphocytes, with the exception of mast cell lines and mast cells, as more recently demonstrated in rodents. Little is known, however, about the capacity of human nonlymphoid cells to produce IL-4. In this study we show that mature human basophils are capable of expressing IL-4 and examine the regulation of IL-4 production in comparison with the lipid mediator leukotriene C4. IL-4 was produced upon immunoglobulin E receptor (IgER) activation of basophils cultured with IL-3, a cytokine previously shown to prime these cells for enhanced release of inflammatory mediators. In some experiments, IL-3 or IgER activation alone also induced IL-4 production close to the detection limit. The effect of IL-3 on IgER-dependent IL-4 expression was dose and time dependent: maximal IL-4 production occurred between 18 and 48 h preexposure of basophils to 3-10 ng/ml IL-3. IgER-induced IL-4 synthesis and release by basophils cultured with IL-3 was rapid and complete after 6 h. In contrast to IL-3, other cytokines (IL-5, granulocyte/macrophage colony-stimulating factor, and nerve growth factor) that also prime basophils for enhanced histamine and leukotriene C4 release did not promote IgER-induced IL-4 synthesis. Basophils appear to secrete a "TH2-like" cytokine profile since no detectable IL-2 or interferon gamma was produced upon IgER activation. Mononuclear cells (depleted of basophils), cultured in parallel, did not release IL-4 in response to IL-3 and/or IgER activation, and produced approximately ten times less IL-4 than basophils upon nonspecific activation by phorbol ester and calcium ionophore. Thus, human basophils are an important cellular source of IL-4, and may, therefore, in addition to their inflammatory effector functions, also regulate the differentiation of T helper cells and B cells, in particular in allergic diseases.