ACTIVATION OF C3B FEEDBACK CYCLE WITH HUMAN COMPLEMENT COMPONENTS .1. THROUGH CLASSICAL PATHWAY

Abstract

Reaction between the 4th, the oxidized 2nd [oxyC2] and the activated 1st components of human complement [c] generated the stable enzyme .**GRAPHIC**. capable of cleaving the 3rd component and depleting total C in human serum. This enzyme was shown further to activate the C3b feedback cycle is shown by its ability to consume factor B in serum and the reduction in the extent of C consumption in the presence of EDTA. OxyC2 on its own gave rise to C3 cleavage in normal human serum by a pathway needing classical pathway components. This unexpected finding suggests that there may be a C.hivin.1 tickover in serum analogous to the C3b tickover; the presence of oxyC2 allowing the capture of the trivial amounts of C42 normally formed. In preliminary experiments in the rat, .**GRAPHIC**. was successfully formed in vivo, where it gave rise to cleavage of C3, consumption of C5, depletion of cobra venom factor cofactors and a biphasic change in the neutrophil count.