The activation of the C3b feedback cycle with human complement components. I. Through the classical pathway.
Reaction between the fourth, the oxidized second and the activated first components of human complement generated the stable enzyme C4oxy2 capable of cleaving the third component and depleting total complement in human serum. This enzyme was shown further to activate the C3b feedback cycle as shown by its ability to consume factor B in serum and the reduction in the extent of complement 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-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, C4oxy2 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.
D000818:Animals; D003166:Complement Activating Enzymes / Q000096:biosynthesis / Q000378:metabolism*; D003172:Complement C1 / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism*; D003184:Complement C7 / Q000378:metabolism; D011415:Complement Factor B; D004306:Dose-Response Relationship, Immunologic; D005246:Feedback; D006461:Hemolysis; D006801:Humans; D051381:Rats
D003172:Complement C1; D003176:Complement C3; D003184:Complement C7; D003179:Complement C3b; D003166:Complement Activating Enzymes; D011415:Complement Factor B