Izumi S, Hirai K, Miyamasu M, Takahashi Y, Misaki Y, Takaishi T, Morita Y, Matsushima K, Ida N, Nakamura H, Kasahara T, Ito K
Department of Medicine and Physical Therapy, University of Tokyo School of Medicine, Japan.
Eur J Immunol. 1997 Apr;27(4):816-24. doi: 10.1002/eji.1830270404.
Several recent studies have identified eosinophils as a cellular source of various cytokines, indicating that eosinophils play not only an effector role, but also a regulatory role within the allergic inflammatory cell network. In this study, we demonstrate that eosinophils can generate and secrete monocyte chemoattractant protein-1 (MCP-1), a prototype of C-C chemokines. Eosinophils generated immunoreactive MCP-1 in response to such diverse stimuli as C5a, formyl-methionyl-leucyl-phenylalanine (FMLP) and ionomycin, but MCP-1 production was not induced by interleukin (IL)-1 or tumor necrosis factor-alpha. C5a- and FMLP-induced eosinophil MCP-1 production was absolutely dependent on pretreatment with cytochalasin B. Eosinophils elaborated significantly more MCP-1 than neutrophils. Immunoreactive MCP-1 was detected at 6 h of incubation with C5a or FMLP. Expression of MCP-1 mRNA reached a maximum within the first 3 h after stimulation and then declined rapidly to a very low and stable level by 18 h. Pretreatment with IL-5 markedly amplified C5a-induced MCP-1 production, and the enhancement occurred at the pretranslational level. Eosinophil-active chemokines such as eotaxin failed to induce MCP-1 generation, even when eosinophils were primed by IL-5. Since MCP-1 exerts a potent histamine-releasing effect on human basophils, our results indicate that eosinophils may regulate basophil mediator release with possible consequent contribution to the pathogenesis of allergic inflammation via a paracrine mechanism.
最近的几项研究已确定嗜酸性粒细胞是多种细胞因子的细胞来源，这表明嗜酸性粒细胞不仅在过敏性炎症细胞网络中发挥效应作用，还发挥调节作用。在本研究中，我们证明嗜酸性粒细胞能够产生并分泌单核细胞趋化蛋白-1（MCP-1），即C-C趋化因子的一个原型。嗜酸性粒细胞在受到诸如C5a、甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）和离子霉素等多种刺激时会产生免疫反应性MCP-1，但白细胞介素（IL）-1或肿瘤坏死因子-α不会诱导MCP-1的产生。C5a和FMLP诱导的嗜酸性粒细胞MCP-1产生绝对依赖于用细胞松弛素B进行预处理。嗜酸性粒细胞产生的MCP-1明显多于中性粒细胞。在与C5a或FMLP孵育6小时时检测到免疫反应性MCP-1。MCP-1 mRNA的表达在刺激后的前3小时内达到最大值，然后在18小时时迅速下降至非常低且稳定的水平。用IL-5预处理可显著增强C5a诱导的MCP-1产生，且这种增强发生在翻译前水平。即使嗜酸性粒细胞用IL-5进行了预激活，嗜酸性粒细胞活性趋化因子如嗜酸性粒细胞趋化因子也未能诱导MCP-1的产生。由于MCP-1对人嗜碱性粒细胞具有强大的组胺释放作用，我们的结果表明嗜酸性粒细胞可能通过旁分泌机制调节嗜碱性粒细胞介质的释放，这可能对过敏性炎症的发病机制有相应的贡献。
