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PubMed · 16204243

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
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Abstract

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.

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AnaphylatoxinsAnimalsAnti-Inflammatory AgentsBone Marrow CellsChemotaxisCloning, MolecularComplement C5aDNA, ComplementaryFemaleGTP-Binding ProteinsGene Expression RegulationInflammationInterleukin-6LungLung InjuryMaleMiceMice, Inbred C57BLMice, TransgenicModels, GeneticNeutrophilsPhenotypeProtein BindingRNA, MessengerReceptor, Anaphylatoxin C5aReceptors, ChemokineRecombinant ProteinsTumor Necrosis Factor-alphaUp-RegulationJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't

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Norma P Gerard, Bao Lu, Pixu Liu, Stewart Craig, Yuko Fujiwara, Shoji Okinaga, Craig Gerard. 2005-10-04. An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2.. https://doi.org/10.1074/jbc.c500287200

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