The anaphylatoxins C3a and C5a play important roles as mediators of inflammation and they regulate and control multiple innate and adaptive immune responses. The effector and regulatory functions of these anaphylatoxins are mediated through binding and activation of their cognate G protein-coupled receptors, including C3a receptor (C3aR), C5a receptor 1 (C5aR1) and C5a receptor 2 (C5aR2). C3aR is the receptor for the chemotactic and inflammatory peptide anaphylatoxin C3a and it stimulates chemotaxis, granule enzyme release, and superoxide anion production. C5aR1 is the receptor for anaphylatoxin C5a while C5aR2 is the receptor for C3a, C4a, and C5a. The activation of C5aR1 stimulates chemotaxis, granule enzyme release, intracellular calcium release, and superoxide anion production. C5aR2 is a modulator of C5AR1 signaling, exerting either anti- or pro-inflammatory activities.
Based on their pleiotropic functions, these anaphylatoxin receptors contribute not only to tissue homeostasis but drive, perpetuate and resolve immune responses in many inflammatory diseases including infections, malignancies, autoimmune as well as allergic diseases. Due to their contribution to different diseases, these receptors represent attractive drug targets and there is great promise for the development of anaphylatoxin receptor-targeted therapeutics in the future. Here, we give an introduction to the human anaphylatoxin chemotactic receptor members about their structure, regulation, biological roles, implications in disease states, and drug discovery.
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