TY - JOUR
T1 - An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2
AU - Gerard, Norma P.
AU - Lu, Bao
AU - Liu, Pixu
AU - Craig, Stewart
AU - Fujiwara, Yuko
AU - Okinaga, Shoji
AU - Gerard, Craig
PY - 2005/12/2
Y1 - 2005/12/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=28844434626&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=28844434626&partnerID=8YFLogxK
U2 - 10.1074/jbc.C500287200
DO - 10.1074/jbc.C500287200
M3 - Article
C2 - 16204243
AN - SCOPUS:28844434626
VL - 280
SP - 39677
EP - 39680
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 48
ER -