Chitin elicits CCL2 from airway epithelial cells and induces CCR2-dependent innate allergic inflammation in the lung.
Chitin elicits CCL2 from airway epithelial cells and induces CCR2-dependent innate allergic inflammation in the lung.
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DOI：
10.4049/jimmunol.1200689
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发表时间：
2012-09-01
期刊：
影响因子：
--
通讯作者：
Klein BS
中科院分区：
文献类型：
--
作者：
Roy RM;Wüthrich M;Klein BS
肺中的甲壳素暴露诱导嗜酸性粒细胞增多和巨噬细胞的交替活化，并且与过敏性气道疾病相关。然而，几丁质诱导的巨噬细胞极化的机制知之甚少。在这里，我们表明，甲壳素诱导体内巨噬细胞的替代激活，但不直接在体外。我们进一步表明，气道上皮细胞在体外结合几丁质，并在体外和体内响应几丁质产生CCL 2。甲壳素暴露的上皮细胞的上清液促进了体外巨噬细胞的交替激活，而抗体中和上清液中的CCL2废除了巨噬细胞的交替激活。CCL2在体内的作用是多余的，但缺乏CCL2受体CCR2的小鼠表现出对几丁质的响应，如通过几丁质酶I、CCL17和CCL22表达所测量的，巨噬细胞的替代活化受损。此外，暴露于几丁质的CCR2KO小鼠肺中的ROS产物减少，嗜酸性粒细胞和单核细胞募集减弱，嗜酸性粒细胞功能受损，如通过CCL5，IL 13和CCL11的表达所测量的。因此，气道上皮细胞分泌CCL2响应几丁质和CCR2信号转导介导几丁质诱导的巨噬细胞和过敏性炎症的交替激活在体内。
Chitin exposure in the lung induces eosinophilia and alternative activation of macrophages, and is correlated with allergic airway disease. However, the mechanism underlying chitin-induced polarization of macrophages is poorly understood. Here, we show that chitin induces alternative activation of macrophages in vivo, but does not do so directly in vitro. We further show that airway epithelial cells bind chitin in vitro and produce CCL2 in response to chitin both in vitro and in vivo. Supernatants of chitin exposed epithelial cells promoted alternative activation of macrophages in vitro, whereas antibody neutralization of CCL2 in the supernate abolished the alternative activation of macrophages. CCL2 acted redundantly in vivo, but mice lacking the CCL2 receptor, CCR2, showed impaired alternative activation of macrophages in response to chitin, as measured by arginase I, CCL17 and CCL22 expression. Furthermore, CCR2KO mice exposed to chitin had diminished ROS products in the lung, blunted eosinophil and monocyte recruitment, and impaired eosinophil functions as measured by expression of CCL5, IL13 and CCL11. Thus, airway epithelial cells secrete CCL2 in response to chitin and CCR2 signaling mediates chitin-induced alternative activation of macrophages and allergic inflammation in vivo.
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