Atypical complement receptor C5aR2 transports C5a to initiate neutrophil adhesion and inflammation
Atypical complement receptor C5aR2 transports C5a to initiate neutrophil adhesion and inflammation
复制标题
DOI：
10.1126/sciimmunol.aav5951
复制
发表时间：
2019-05-01
影响因子：
24.8
通讯作者：
Luster, Andrew D.
中科院分区：
文献类型：
--
作者：
Miyabe, Yoshishige;Miyabe, Chie;Luster, Andrew D.
趋化因子诱导的循环白细胞停滞及其随后的渗出是炎症的基本组成部分。然而，组织来源的化学引诱物如何被运输到血管腔中以诱导白细胞进入组织中还没有很好地理解。在此，活小鼠活体显微镜检查显示，在免疫复合物诱导的关节炎小鼠模型中，内皮细胞上表达的“非典型”补体C5a受体2（C5aR2）和非典型趋化因子受体1（ACKR1）分别是C5a和CXCR2趋化因子配体转运到血管腔中所需的。需要转运的C5a来启动C5aR1介导的中性粒细胞停滞，而需要转运的趋化因子来启动CXCR2依赖的中性粒细胞跨内皮迁移。这些发现提供了非典型化学引诱物受体如何与“经典”信号化学引诱物受体合作，以控制中性粒细胞招募到炎症组织部位的不同步骤的见解。
Chemoattractant-induced arrest of circulating leukocytes and their subsequent diapedesis is a fundamental component of inflammation. However, how tissue-derived chemoattractants are transported into the blood vessel lumen to induce leukocyte entry into tissue is not well understood. Here, intravital microscopy in live mice has shown that the "atypical" complement C5a receptor 2 (C5aR2) and the atypical chemokine receptor 1 (ACKR1) expressed on endothelial cells were required for the transport of C5a and CXCR2 chemokine ligands, respectively, into the vessel lumen in a murine model of immune complex-induced arthritis. Transported C5a was required to initiate C5aR1-mediated neutrophil arrest, whereas transported chemokines were required to initiate CXCR2-dependent neutrophil transdendothelial migration. These findings provide insights into how atypical chemoattractant receptors collaborate with "classical" signaling chemoattractant receptors to control distinct steps in the recruitment of neutrophils into tissue sites of inflammation.