PubMed1990
C3, the most abundant complement protein in blood, plays a central role in the activation sequence of the complement system as well as in host defense. Expression of the multiple functions of C3 requires its cleavage by highly specific enzymes termed C3 convertases. C3 in a conformationally altered form, C3H2O, resulting from the slow spontaneous hydrolysis of the internal thioester bond of native C3, initiates the assembly of a C3 convertase which continuously cleaves C3 in the blood at slow rates generating a constant supply of small amounts of C3b. When an activator of the alternative complement pathway is present, C3b becomes covalently attached to its surface via an ester or amide bond. Activator surface-bound C3b initiates the assembly of an "amplification" C3 convertase, C3bBb(P), which can efficiently activate C3 and generate additional convertase complexes on the surface of the activator. C3b generated by an amplification or classical pathway C3 convertase can also bind covalently to the noncatalytic subunit, C3b or C4b, respectively, resulting in the generation of a C5 convertase, an enzyme catalyzing the cleavage/activation of C5. In terms of participation in host defense, several fragments of C3, including C3a, C3b, iC3b, and C3dg, mediate a number of important functions such as increased vascular permeability, enhancement of phagocytosis, elimination of immune complexes, and perhaps also proliferative responses and/or differentiation of B cells.