Anaphylatoxine

Anaphylatoxins are small peptide mediators generated during activation of the complement system. The term normally refers to the fragments C3a, C4a, and C5a, produced by proteolytic cleavage of the complement components C3, C4, and C5 during classical, lectin, or alternative pathway activation. These mediators act locally to amplify inflammation and coordinate innate immune responses.

C5a is the most potent anaphylatoxin, acting as a strong chemoattractant for neutrophils and monocytes and as a potent activator of inflammatory cells. C3a and C4a contribute to inflammatory responses as well, promoting mast cell and basophil degranulation and histamine release. The effects of anaphylatoxins are mediated through G protein-coupled receptors: C3a binds to the C3a receptor (C3aR), while C5a binds to C5a receptor 1 (C5aR1, CD88) and to the receptor C5L2 (GPR77), whose signaling role is less clear.

Inactivation of anaphylatoxins occurs mainly through carboxypeptidase enzymes that remove the C-terminal arginine, forming des-Arg-C3a and des-Arg-C5a, which have markedly reduced activity. C4a is generally less active, and its des-Arg form is even less so.

Clinical relevance and therapeutic context: excessive production of anaphylatoxins can contribute to inflammatory pathology in conditions such as sepsis, acute lung injury, and autoimmune disorders. Therapeutic approaches include complement inhibition at various steps (for example, preventing C5 cleavage) and antagonism of C5a receptors to dampen harmful inflammation while preserving host defense.