Human Complement 5a (C5a) is an enzymatically generated glycoprotein that belongs to a family of structurally and functionally related proteins known as anaphylatoxins. C5a is a 74 amino acid (aa) peptide that is created by the activity of C5a convertase on the C5 α-chain. Human C5a has four α-helices plus three intrachain disulfide bonds that create a triple loop structure. Human C5a is 60% and 54% aa identical to mouse and rat C5a, respectively. C5a binds to a signaling G-protein coupled receptor (C5aR/CD88) and a nonsignaling GPCR termed C5L2. Activation of Cd88 results in neutrophil chemotaxis and endothelial cell activation. It also triggers an oxidative burst in macrophages and neutrophils, and induces release of histamine in basophils and mast cells.