Complement C5a
The 74 amino acid transmembrane glycoprotein, complement C5a (C5a), is a potent pro-inflammatory mediator cleaved enzymatically from its precursor, C5, upon activation of the complement cascade. C5a is a member of the anaphylatoxin family of three proteins (C3a, C4a, and C5a) produced by the activation of the complement cascade. C5a is quickly metabolised by carboxypeptidases, forming the less potent C5adesArg. C5a has been found to be a significant pathogenic driver in a number of immuno-inflammatory diseases, making C5a inhibition an attractive therapeutic strategy. C5a is a strong chemoattractant and is involved in the recruitment of inflammatory cells such as neutrophils, eosinophils, monocytes, and T lymphocytes, in activation of phagocytic cells and release of granule-based enzymes and generation of oxidants, all of which may contribute to innate immune functions or tissue damage. Particularly abundant transcripts for the C5a receptor are found in lung, spleen, heart, placenta, spinal cord and throughout the brain. Dysregulated C5a-mediated inflammation contributes to autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, epidermolysis bullosa acquisita, antiphospholipid syndrome, and others. C5a also participates in the pathogenesis of cancer, neurodegenerative diseases, sepsis, ischemia-repurfusion injury, and many other inflammatory diseases.
