Complement Anaphylatoxins (C3a, C4a, C5a) and Their Receptors (C3aR, C5aR/CD88) as Therapeutic Targets in Inflammation

One of the major biological consequences of complement activation is the generation of three small cationic peptides C3a, C4a, and C5a collectively referred to as complement anaphylatoxins. The word anaphylatoxin was first used by Friedberger to describe the activity found in complement-activated serum, which produced rapid death when injected into laboratory animals (1). It has remained the generic name given to these peptides. As a group, the complement anaphylatoxins are recognized for their potent proinflammatory functions in mediating smooth muscle contraction, histamine release from mast cells, and increased vascular permeability (2–6). In addition, one of the peptides, C5a, is recognized as one of the most potent molecular chemoattractants for neutrophils and other leukocytes (7). The other two peptides, C3a and C4a, were considered for a time not to exhibit any chemoattractant properties; however, during the past few years it has become clear that C3a, although not chemoattractant for neutrophils (8), can cause the directed migration of eosinophils (8), and possibly mast cells (9,10). Presently, it is unclear if C4a is also a chemoattractant molecule.