Evidence That Cobra Venom Factor (CoF) Is Cobra C3

Abstract The presence in cobra venom of an anticomplementary activity has been known for over 80 years. More recent studies have demonstrated that purified CoF incubated with mammalian sera results in an alternative pathway mediated attack on C3. Lachmann and Nicol have pointed out that CoF is “C3b-like” in its ability to activate C3 and later components. The present studies strongly suggest that CoF is, in fact, altered cobra C3. Potent rabbit antiserum to CoF cross-reacts with human C3. On immunofixation of cobra serum after prolonged agarose gel electrophoresis, a single reactive band was found in the β1-region. Multiple slower bands were found in cobra venom or purified CoF, suggesting that CoF is an altered form of the serum molecule. When cobra serum was incubated at 37°C, slow conversion to a more rapidly migrating form was observed in immunoelectrophoresis. Much more rapid conversion occurred when cobra serum was incubated with endotoxin at 37°C. No alteration in the mobility of CoF incubated with purified human C3b inactivator was observed, nor was there reduction in its ability to inactivate C3 in normal human serum. However, incubation with cobra serum destroyed the capacity of CoF to induce C3 conversion in human serum. These observations suggest that CoF is altered cobra C3 which has the capacity, like human C3b, to activate the alternative pathway. Its very potent C3-inactivating activity derives from the fact that CoF is not inactivated by mammalian C3b inactivator.