C5L2 is critical for the biological activities of the anaphylatoxins C5a and C3a

被引:193
作者
Chen, Nien-Jung
Mirtsos, Christine
Suh, Daniel
Lu, Yong-Chen
Lin, Wen-Jye
McKerlie, Colin
Lee, Taeweon
Baribault, Helene
Tian, Hui
Yeh, Wen-Chen [1 ]
机构
[1] Univ Toronto, Univ Hlth Network, Ontario Canc Inst, Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2C1, Canada
[2] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2C1, Canada
[3] Hosp Sick Children, Toronto, ON M5G 1X8, Canada
[4] Amgen San Francisco, San Francisco, CA 94080 USA
基金
加拿大健康研究院;
关键词
D O I
10.1038/nature05559
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Complement-derived anaphylatoxins regulate immune and inflammatory responses through G-protein-coupled receptor ( GPCR)mediated signalling(1-4). C5L2 ( also known as GPR77) is a relatively new GPCR thought to be a non-signalling receptor binding to C5a, on the basis of sequence information and experimental evidence(5-7). Here we show, using gene targeting, that C5L2 is required to facilitate C5a signalling in neutrophils, macrophages and fibroblasts in vitro. Deficiency of C5L2 results in reduced inflammatory cell infiltration, suggesting that C5L2 is critical for optimal C5a-mediated cell infiltration in certain in vivo settings. C5L2 is also involved in optimizing C3a-induced signals. Furthermore, like mice incapable of C3a/complement 3a receptor (C3aR) signalling(4,8,9), C5L2-deficient mice are hypersensitive to lipopolysaccharide (LPS)-induced septic shock, show reduced ovalbumin (OVA)-induced airway hyperresponsiveness and inflammation, and are mildly delayed in haematopoietic cell regeneration after gamma-irradiation. Our data indicate that C5L2 can function as a positive modulator for both C5a- and C3a-anaphylatoxin-induced responses.
引用
收藏
页码:203 / 207
页数:5
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