Complement C3a
Natural human complement C3a (C3a) is prepared by cleavage of human C3 protein by a human C3 convertase. C3a is a member of the anaphylatoxin family of three proteins (C3a, C4a, and C5a) produced by the activation of the complement cascade. C3a is a 77 amino acid transmembrane protein that mediates many inflammatory responses including smooth muscle contraction, vasodilation, increased vascular permeability, and release of histamine from mast cells and basophils. C3a has been reported to exert effects in mast cells, macrophages/monocytes, T cells, and APCs. It induces calcium mobilization from intracellular stores, activation of extracellular signal-regulated kinases (ERK)1/2, and release of extracellular adenosine triphosphate (ATP) in monocytes and macrophages. C3a has immunomodulatory functions including degranulation of eosinophils, basophils, and mast cells. C3a acts through the C3a Receptor (C3aR) which is a G-protein coupled receptor found widely distributed on peripheral tissues, lymphoid cells (neutrohphils, monocytes, and eosinophils) and in the central nervous system (astrocytes, neurons and glial cells). C3a receptors are abundant, specifically, in lung, spleen, ovary, placenta, small intestine and less ubiquitously in the brain. C3a participates in the pathogenesis of various diseases including Alzeimers disease, asthma, coronary artery disease, cancer, arthritis, sepsis, ischemia-repurfusion injury, and various kidney diseases including glomerular diseases and tubulointerstitial diseases.
