C5L2 is critical for the biological activities of the anaphylatoxins C5a and C3a
C5L2 is critical for the biological activities of the anaphylatoxins C5a and C3a
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DOI：
10.1038/nature05559
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发表时间：
2007-03-08
期刊：
影响因子：
64.8
通讯作者：
Yeh, Wen-Chen
中科院分区：
文献类型：
--
作者：
Chen, Nien-Jung;Mirtsos, Christine;Yeh, Wen-Chen
补体衍生的过敏毒素通过G蛋白偶联受体（GPCR）介导的信号传导调节免疫和炎症反应（1-4）。C5 L2（也称为GPR 77）是一种相对较新的GPCR，根据序列信息和实验证据，认为是与C5 a结合的非信号传导受体（5-7）。在这里，我们表明，使用基因靶向，C5 L2是需要促进C5 a信号在体外中性粒细胞，巨噬细胞和成纤维细胞。C5 L2的缺乏导致炎性细胞浸润减少，表明C5 L2对于某些体内环境中的最佳C5 a介导的细胞浸润至关重要。C5 L2还参与优化C3 a诱导的信号。此外，与不能进行C3 a/补体3a受体（C3 aR）信号传导的小鼠一样（4，8，9），C5 L2缺陷小鼠对脂多糖（LPS）诱导的脓毒性休克超敏，显示卵清蛋白（OVA）诱导的气道高反应性和炎症降低，并且在γ-照射后造血细胞再生轻度延迟。我们的数据表明，C5 L2可以作为一个积极的调制器C5 a和C3 a过敏毒素诱导的反应。
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.