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

Norma P. Gerard, Bao Lu, Pixu Liu, Stewart Craig, Yuko Fujiwara, Shoji Okinaga, Craig Gerard
2005 Journal of Biological Chemistry  
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
more » ... ring 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.
doi:10.1074/jbc.c500287200 pmid:16204243 fatcat:4aoskhmeqjfg5i6h5t34liv3ii