An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2.
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.
Pubmed ID: 16204243 RIS Download
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