Characterization of a C3/C3b regulatory protein in normal human serum.

A protein which alters the activity of C3 and C3b has been isolated from normal human serum by sequential column chromatography. In purified form, at normal serum concentration, this protein fixes to cell-bound C3b. It cannot bind to C3d. After fixation, it prevents the inactivation of C3b by beta 1H and C3bINA in both the classical and alternative pathway C5 convertases. Independent of this action, fixation to C3b also markedly enhances the subsequent activity of C5. At higher concentrations, however, this protein is capable of blocking the activation of C3 by both pathway C3 convertases. This material, therefore, appears to represent a potent means of regulating several critical aspects of the biologic activity of the complement system.