An Anti-inflammatory Function for the Complement Anaphylatoxin C5a-binding Protein, C5L2

• Published in: The Journal of biological chemistry 2005-12, Vol.280 (48), p.39677-39680
• Main Authors: Gerard, Norma P., Lu, Bao, Liu, Pixu, Craig, Stewart, Fujiwara, Yuko, Okinaga, Shoji, Gerard, Craig
• Format: Article
• Language: English
• Subjects: Anaphylatoxins - chemistry; Animals; Anti-Inflammatory Agents - pharmacology; Bone Marrow Cells - metabolism; Chemotaxis; Cloning, Molecular; Complement C5a - chemistry; DNA, Complementary - metabolism; Female; Gene Expression Regulation; GTP-Binding Proteins - metabolism; Inflammation; Interleukin-6 - biosynthesis; Lung - pathology; Lung Injury; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Genetic; Neutrophils - metabolism; Phenotype; Protein Binding; Receptor, Anaphylatoxin C5a; Receptors, Chemokine - genetics; Receptors, Chemokine - physiology; Recombinant Proteins - chemistry; RNA, Messenger - metabolism; Tumor Necrosis Factor-alpha - biosynthesis; Up-Regulation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.C500287200

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/C5adesArg 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.