Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation.
Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation.
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巨噬细胞改变非专职吞噬细胞的吞噬作用，并影响炎症。
DOI：
10.1038/nature20141
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发表时间：
2016-11-24
期刊：
影响因子：
64.8
通讯作者：
Ravichandran KS
中科院分区：
文献类型：
--
作者：
Han CZ;Juncadella IJ;Kinchen JM;Buckley MW;Klibanov AL;Dryden K;Onengut-Gumuscu S;Erdbrügger U;Turner SD;Shim YM;Tung KS;Ravichandran KS
专职吞噬细胞（如巨噬细胞）和非专职吞噬细胞（如上皮细胞）每天清除数十亿凋亡细胞和颗粒。由于这些吞噬细胞存在于大多数组织中，因此在细胞清除过程中它们之间是否存在交叉通信，以及这可能如何影响炎症尚不清楚。在这里，我们表明，巨噬细胞，通过释放可溶性生长因子和微泡，重定向的类型的颗粒吞噬的非专业吞噬细胞和影响他们的炎症反应。在凋亡细胞吞噬或炎症相关细胞因子的反应中，巨噬细胞释放胰岛素样生长因子1（IGF-1）。IGF-1与其在非专职吞噬细胞上的受体的结合重新定向了它们的吞噬作用，使得较大凋亡细胞的摄取被抑制，而微泡的吞噬被增强。巨噬细胞对这种IGF-1介导的吞噬调节不敏感。巨噬细胞还释放微泡，其被上皮细胞摄取，通过IGF-1增强，导致上皮细胞的炎症反应降低。与这些观察结果一致，气道上皮细胞中IGF-1受体的缺失导致过敏原暴露后肺部炎症加重。这些遗传和功能研究揭示了巨噬细胞和上皮细胞之间的新型IGF-1和微泡依赖性通信，其可以严重影响体内组织炎症的程度。
Professional phagocytes (such as macrophages) and non-professional phagocytes (such as epithelial cells) clear billions of apoptotic cells and particles on a daily basis. Since these phagocytes reside in proximity in most tissues, whether cross-communication exists between them during cell clearance, and how this might impact inflammation are not known. Here, we show that macrophages, via the release of a soluble growth factor and microvesicles, redirect the type of particles engulfed by non-professional phagocytes and influence their inflammatory response. During apoptotic cell engulfment or in response to inflammation-associated cytokines, macrophages released insulin-like growth factor 1 (IGF-1). The binding of IGF-1 to its receptor on non-professional phagocytes redirected their phagocytosis, such that uptake of larger apoptotic cells was dampened while engulfment of microvesicles was enhanced. Macrophages were refractory to this IGF-1 mediated engulfment modulation. Macrophages also released microvesicles, whose uptake by epithelial cells, enhanced by IGF-1, led to decreased inflammatory responses by epithelial cells. Consistent with these observations, deletion of IGF-1 receptor in airway epithelial cells led to exacerbated lung inflammation after allergen exposure. These genetic and functional studies reveal a novel IGF-1 and microvesicle-dependent communication between macrophages and epithelial cells that can critically influence the magnitude of tissue inflammation in vivo.
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