Production of the novel C-C chemokine MCP-4 by airway cells and comparison of its biological activity to other C-C chemokines
Production of the novel C-C chemokine MCP-4 by airway cells and comparison of its biological activity to other C-C chemokines
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DOI：
10.1172/jci119257
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发表时间：
1997-03-01
影响因子：
15.9
通讯作者：
Schleimer, RP
中科院分区：
文献类型：
--
作者：
Stellato, C;Collins, P;Schleimer, RP
单核细胞趋化蛋白 4 (MCP-4) 是一种新鉴定的 C-C 趋化因子，具有有效的嗜酸性粒细胞趋化特性。我们描述了其体外生物活性的研究，以诱导外周血嗜酸性粒细胞的趋化性并诱导 IL-3 引发的外周血嗜碱性粒细胞释放组胺。 MCP-4 和嗜酸性粒细胞趋化因子引起类似的嗜酸性粒细胞胞浆内 Ca2+ 升高和完全交叉脱敏。 MCP-4 还消除了嗜酸性粒细胞 Ca2+ 对 MCP-3 的反应，并部分降低了对巨噬细胞炎症蛋白 1 α 的反应。在转染这些趋化因子受体的小鼠淋巴瘤细胞中，MCP-4 通过 CCR2b 或 CCR3 激活细胞迁移。 MCP-4 抑制 I-125-eotaxin 与嗜酸性粒细胞和 CCR3 转染细胞的结合，并抑制 I-125-MCP-1 与 CCR2b 转染子的结合。在哮喘和非哮喘受试者的支气管肺泡灌洗液中收集的细胞中发现了 MCP-4 mRNA，并且在人肺和心脏中显着表达。细胞因子刺激后，MCP-4 mRNA 在几种人支气管上皮细胞系中表达。用糖皮质激素布地奈德预处理 BEAS-2B 上皮细胞可抑制 MCP-4 mRNA 表达。这些特征使 MCP-4 成为在过敏性呼吸道疾病期间在嗜酸性粒细胞募集中发挥作用的候选者。
Monocyte chemotactic protein-4 (MCP-4) is a newly identified C-C chemokine with potent eosinophil chemoattractant properties. We describe studies of its biological activity in vitro to induce chemotaxis of peripheral blood eosinophils and to induce histamine release from IL-3-primed peripheral blood basophils. MCP-4 and eotaxin caused a similar rise in eosinophil intracytoplasmic Ca2+ and complete cross-desensitization. MCP-4 also abolished the eosinophil Ca2+ response to MCP-3 and partially desensitized the response to macrophage inflammatory protein-1 alpha. MCP-4 activated cell migration via either CCR2b or CCR3 in mouse lymphoma cells transfected with these chemokine receptors. MCP-4 inhibited binding of I-125-eotaxin to eosinophils and CCR3-transfected cells and inhibited I-125-MCP-1 binding to CCR2b-transfectants. MCP-4 mRNA was found in cells collected in bronchoalveolar lavage of asthmatic and nonasthmatic subjects and was prominently expressed in human lung and heart. MCP-4 mRNA was expressed in several human bronchial epithelial cell lines after cytokine stimulation. Pretreatment of BEAS-2B epithelial cells with the glucocorticoid budesonide inhibited MCP-4 mRNA expression. These features make MCP-4 a candidate for playing a role in eosinophil recruitment during allergic respiratory diseases.