An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2.
Journal:
J. Biol. Chem. 2005 DecAuthors:
Gerard NP, Lu B, Liu P, Craig S, Fujiwara Y, Okinaga S, Gerard C
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 bea
...[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.[less]
Mesh Headings:
Anaphylatoxins, Animals, Anti-Inflammatory Agents, Bone Marrow Cells, Chemotaxis, Cloning, Molecular, Complement C5a, DNA, Complementary, Female, GTP-Binding Proteins, Gene Expression Regulation, Inflammation, Interleukin-6, Lung, Lung Injury, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Genetic, Neutrophils, Phenotype, Protein Binding, RNA, Messenger, Receptors, Chemokine, Recombinant Proteins, Tumor Necrosis Factor-alpha, Up-Regulation