Complement components C3a and C5a (C3a/C5a)

Complement components C3a and C5a, collectively known as anaphylatoxins, are potent pro-inflammatory peptides generated during the activation of the complement cascade [1, 4]. They are produced through the enzymatic cleavage of the central complement proteins C3 and C5 by their respective convertases [5, 7]. C3a and C5a exert their biological effects by binding to specific G protein-coupled receptors (GPCRs), namely C3aR, C5aR1 (CD88), and C5aR2 (C5L2), which are widely expressed on immune cells such as neutrophils, macrophages, and mast cells [3, 6]. These molecules play a critical role in the innate immune response by promoting chemotaxis, increasing vascular permeability, and inducing the release of inflammatory mediators [2, 17]. In various disease states, including autoimmune disorders, sepsis, and cancer, the overactivation of the C3a and C5a signaling axes contributes to tissue damage and immunosuppression within the tumor microenvironment [11, 14]. Consequently, they have emerged as significant therapeutic targets, with drugs like avacopan and vilobelimab designed to block their signaling to treat conditions such as ANCA-associated vasculitis and severe inflammatory responses [9, 13].

Other names

AnaphylatoxinsC3aC5aComplement component 3aComplement component 5aC3a-desArgC5a-desArg

Inhibition of the anaphylatoxin signaling pathway through either the direct neutralization of C3a and C5a ligands or the antagonism of their cognate receptors (C3aR and C5aR1), thereby preventing the recruitment and activation of inflammatory cells [9, 13].