Gerard Norma P, Lu Bao, Liu Pixu, Craig Stewart, Fujiwara Yuko, Okinaga Shoji, Gerard Craig
Pulmonary Division, Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Biol Chem. 2005 Dec 2;280(48):39677-80. doi: 10.1074/jbc.C500287200. Epub 2005 Oct 4.
C5L2 is an enigmatic serpentine receptor that is co-expressed with the C5a receptor on many cells including polymorphonuclear neutrophils. The apparent absence of coupling of C5L2 with G proteins suggests that this receptor may modulate the biological activity of C5a, perhaps by acting as a decoy receptor. Alternatively, C5L2 may affect C5a function through formation of a heteromeric complex with the C5aR, or it may utilize a G protein-independent signaling pathway. Here we show that in mice bearing a targeted deletion of C5L2, the biological activity of C5a/C5a(desArg) is enhanced both in vivo and in vitro. The biological role of C5L2 thus appears to be limiting to the pro-inflammatory response to the anaphylatoxin. Accordingly, up-regulation of C5L2 may be of benefit in inflammatory states driven by C5a, including sepsis, asthma, cystic fibrosis, and chronic obstructive lung disease.
C5L2是一种神秘的蛇形受体，它与C5a受体在包括多形核中性粒细胞在内的许多细胞上共同表达。C5L2与G蛋白明显缺乏偶联，这表明该受体可能通过充当诱饵受体来调节C5a的生物学活性。或者，C5L2可能通过与C5aR形成异源复合物来影响C5a功能，或者它可能利用不依赖G蛋白的信号通路。在这里我们表明，在C5L2基因靶向缺失的小鼠中，C5a/C5a(去精氨酸)的生物学活性在体内和体外均增强。因此，C5L2的生物学作用似乎是限制对过敏毒素的促炎反应。相应地，C5L2的上调可能对由C5a驱动的炎症状态有益，包括败血症、哮喘、囊性纤维化和慢性阻塞性肺疾病。
