The natural modulation of the amplification phase of complement activation

Abstract

As C3 cleavage represents the most critical step in the elaboration of the biologic effects of the complement system, the modulation of this reaction by formation and function of the C3b-dependent C3 convertase may well determine whether the initial activation of the complement sequence eventuates in beneficial or detrimental effects to the host. Stabilization of the amplification C3b-dependent convertase, C3bBb, is achieved with P and C3NeF, respectively, after their binding which exhibits different molecular and temperature requirements. Control of this amplifying step occurs at three levels: intrinsic decay of the inherently labile C3bBb convertase; extrinsic decay by displacement of Bb from the convertase with beta1H; and inactivation by C3bINA of C3b after its generation from native C3 or removal of protective Bb by intrinsic or extrinsic decay. In the presence of the stabilizing factors the control proteins must function in sequence with beta1H-mediated decay preceding C3b inactivation.