C5a anaphylatoxin receptor 1 (C5aR1)

The C5a anaphylatoxin receptor 1 (C5aR1), also known as CD88, is a high-affinity G protein-coupled receptor that mediates the potent pro-inflammatory effects of the complement cleavage product C5a [1, 2]. Primarily expressed on neutrophils, monocytes, and macrophages, C5aR1 activation triggers cellular chemotaxis, degranulation, and the release of inflammatory cytokines and reactive oxygen species [1, 4]. This receptor plays a critical role in the pathogenesis of various inflammatory and autoimmune disorders, most notably anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, where it drives leukocyte recruitment and vascular damage [3, 5]. Therapeutically, C5aR1 is targeted by small molecule antagonists such as avacopan, which block the inflammatory cascade without impairing the formation of the membrane attack complex, thus preserving certain antimicrobial functions [3, 6]. Beyond its primary immune functions, C5aR1 is increasingly recognized for its role in the tumor microenvironment and neuroinflammatory pathways, making it a versatile target for drug development [5, 7]. Sources: [1] UniProt P21730; [2] NCBI Gene ID 728; [3] FDA Tavneos (avacopan) Label; [4] Klos et al. (2013) 'The complement-derived anaphylatoxins'; [5] Jayne et al. (2021) 'Avacopan for the Treatment of ANCA-Associated Vasculitis', NEJM; [6] Monk et al. (2007) 'Function, structure and therapeutic potential of complement C5a receptors'; [7] PubMed ID 33015174.

Other names

Complement component 5a receptor 1CD88C5ARC5R1C5a receptorC5aR

Selective antagonism of the C5a receptor 1, which competitively inhibits the binding of the C5a ligand. This blockade prevents C5a-mediated G protein signaling, effectively inhibiting the chemotaxis and activation of neutrophils and other myeloid cells, thereby reducing complement-driven tissue damage [3, 4, 6].