EFFECTS OF DECOMPLEMENTATION WITH COBRA VENOM FACTOR ON EXPERIMENTAL VASCULITIS

Mercuric chloride (HgCl2) induces autoimmunity in susceptible rat stra ins, with hyper-IgE, appearance of a number of autoantibodies, and wid espread tissue injury, including necrotizing vasculitis in the gut. In the early phase of tissue injury there is granulocyte infiltration; l ater there is immunoglobulin deposition along basement membranes in ve ssels. We have analysed the role of complement in this model using cob ra venom factor (CVF), which causes decomplementation lasting around 5 days. The characteristic time course when HgCl2 is given over 10 days is that tissue injury and autoantibody levels reach a peak at around day 15 (start of HgCl2 = day 0). We therefore gave CVF either early (d ay 0), intermediate (day 5) or late (day 10); a fourth group (controls ) received HgCl2 but no CVF. At each time point, CVF caused complete d ecomplementation which lasted for at least 5 days. Serum IgE and autoa ntibody levels were similar in all four experimental groups. Tissue in jury in the 'early' CVF group and in the 'late' CVF group was not sign ificantly different from controls, but in the intermediate group tissu e injury was significantly more severe than in controls. These data in dicate that the complement system does not play a major role in the in duction of autoantibodies by HgCl2, nor in the effector phase of tissu e injury. We speculate that the exacerbation of tissue injury by CVF i n the group given this agent at an intermediate stage of the model is explained by the presence of products of C3 activation which have proi nflammatory effects during the phase of active granulocyte-mediated ti ssue injury.