C5L2: a controversial receptor of complement anaphylatoxin, C5a

Li, Rui, Coulthard, Liam G., Wu, M. C. L., Taylor, Stephen M. and Woodruff, Trent M. (2013) C5L2: a controversial receptor of complement anaphylatoxin, C5a. FASEB Journal, 27 3: 855-864. doi:10.1096/fj.12-220509

Author Li, Rui
Coulthard, Liam G.
Wu, M. C. L.
Taylor, Stephen M.
Woodruff, Trent M.
Title C5L2: a controversial receptor of complement anaphylatoxin, C5a
Journal name FASEB Journal   Check publisher's open access policy
ISSN 0892-6638
Publication date 2013-03-01
Year available 2013
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1096/fj.12-220509
Open Access Status Not Open Access
Volume 27
Issue 3
Start page 855
End page 864
Total pages 10
Place of publication Bethesda, MD, United States
Publisher Federation of American Societies for Experimental Biology
Language eng
Abstract C5a is the paramount proinflammatory mediator of the complement cascade, and has been previously thought to act only through a single, G-protein- coupled, C5a receptor (C5aR; also termed CD88). In 2000, a second C5a receptor, C5L2 (previously known as GPR77), was discovered; yet, despite 12 yr of intensive research, its biological, or pathophysiological, function is both enigmatic and controversial. Unlike C5aR, this receptor does not couple to G proteins, and early studies promoted the hypothesis that C5L2 functions as a decoy receptor. However, recent data have provided other evidence for more complicated and conflicting interactions between C5L2 and other inflammatory mediators. C5L2 has been recently demonstrated to physically interact with both C5aR and β-arrestin to negatively regulate C5aR signaling toward an anti-inflammatory manner, and to reduce pathology, in several disease models in vivo. In direct contrast, other groups have demonstrated that C5L2 stimulation caused release of HMGB1 both in vitro and in vivo, and enhanced pathology in sepsis models, suggesting a clear proinflammatory signaling role. These astoundingly contradictory data challenge our precepts and complicate the foundational bases for the possible targeting of C5L2 as a therapeutic option in inflammatory disease. C5L2 may be the great masquerader in complement biology; its function dependent on the cell type, species, and disease context. Because of these unusual and unforeseen complexities, we present the current state of knowledge on C5L2 structure, expression and, most controversially, its putative functions.
Keyword Inflammation
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID APP1021413
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
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