Effects of decomplementation with cobra venom factor on experimental vasculitis.
Mercuric chloride (HgCl2) induces autoimmunity in susceptible rat strains, with hyper-IgE, appearance of a number of autoantibodies, and widespread tissue injury, including necrotizing vasculitis in the gut. In the early phase of tissue injury there is granulocyte infiltration; later there is immunoglobulin deposition along basement membranes in vessels. We have analysed the role of complement in this model using cobra 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 (day 0), intermediate (day 5) or late (day 10); a fourth group (controls) received HgCl2 but no CVF. At each time point, CVF caused complete decomplementation which lasted for at least 5 days. Serum IgE and autoantibody levels were similar in all four experimental groups. Tissue injury in the 'early' CVF group and in the 'late' CVF group was not significantly different from controls, but in the intermediate group tissue injury was significantly more severe than in controls. These data indicate that the complement system does not play a major role in the induction of autoantibodies by HgCl2, nor in the effector phase of tissue injury. We speculate that the exacerbation of tissue injury by CVF in the group given this agent at an intermediate stage of the model is explained by the presence of products of C3 activation which have proinflammatory effects during the phase of active granulocyte-mediated tissue injury.
Mathieson
P W
PW
Department of Medicine Unit, University of Cambridge, UK.
Qasim
F J
FJ
Thiru
S
S
Oldroyd
R G
RG
Oliveira
D B
DB
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D015551:Autoimmunity; D003165:Complement System Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000008:administration & dosage / Q000276:immunology*; D007073:Immunoglobulin E / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007279:Injections, Subcutaneous; D008627:Mercuric Chloride / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D014657:Vasculitis / Q000276:immunology*
D001323:Autoantibodies; D004546:Elapid Venoms; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D008627:Mercuric Chloride; D003165:Complement System Proteins