Modulation of Generation of the Amplification Convertase C3b,Bb by Heparin

Abstract

Commercial heparin, a degraded mixture of hog glycosoaminoglycans, inhibits generation of the amplification convertase, C3b, Bb, on a cellular intermediate or in the fluid phase. Heparin is most active in inhibiting convertase generation on cellular intermediates formed with the lowest C3 input and developed with the highest B concentration, suggesting that the point of heparin action is the receptor site for B on C3b. Inhibition is observed also when C3b,Bb generation takes place on cellular intermediates in the presence of P or C3NeF, which yield stabilized forms of the convertase. This inhibitory action of heparin is not due to chelation of magnesium. Fifty times the concentration of heparin required to inhibit convertase generation does not accelerate the decay of the unstabilized or the C3NeF-stabilized convertases and has only a modest effect on the P-stabilized convertase. These studies indicate that in addition to the previously reported sites of heparin inhibition on classical pathway function noted by others, heparin acts to prevent effective interaction of C3b and B, most likely by a reversible action on C3b.