Expression and regulation of monocyte chemoattractant protein-1 by human eosinophils
Expression and regulation of monocyte chemoattractant protein-1 by human eosinophils
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DOI：
10.1002/eji.1830270404
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发表时间：
1997-04-01
影响因子：
5.4
通讯作者：
Ito, K
中科院分区：
文献类型：
--
作者：
Izumi, S;Hirai, K;Ito, K
最近的几项研究发现，嗜酸性粒细胞是各种细胞因子的细胞来源，表明嗜酸性粒细胞不仅扮演着效应者的角色，而且在变态反应性炎症细胞网络中也扮演着调节角色。在这项研究中，我们证明了嗜酸性粒细胞可以产生和分泌单核细胞趋化蛋白-1(MCP-1)，这是C-C趋化因子的原型。嗜酸性粒细胞在C5a、甲硫酰-亮氨酰苯丙氨酸(FMLP)和离子霉素刺激下产生免疫反应MCP-1，而IL-1和肿瘤坏死因子-α不能诱导MCP-1的产生。C5a和FMLP诱导的嗜酸性粒细胞MCP-1的产生完全依赖于细胞松弛素B的预处理，嗜酸性粒细胞表达的MCP-1明显多于中性粒细胞。与C5a或FMLP孵育6h即可检测到MCP-1免疫反应阳性。MCP-1mRNA的表达在刺激后3h达到高峰，18h后迅速下降至一个很低的稳定水平，IL-5可显著增强C5a诱导的MCP-1的产生，且这种增强作用发生在翻译前水平。嗜酸性粒细胞活性趋化因子，如嗜酸性粒细胞趋化因子，即使在嗜酸性粒细胞被IL-5激活的情况下，也不能诱导MCP-1的产生。由于单核细胞趋化蛋白-1对人嗜碱性粒细胞具有强大的组胺释放作用，我们的结果提示嗜酸性粒细胞可能通过旁分泌机制调节嗜碱性粒细胞介体的释放，从而在变态反应性炎症的发病机制中发挥作用。
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.