Depletion of plasma complement in vivo by a protein of cobra venom: its effect on various immunologic reactions

Abstract

The purified low molecular weight anticomplementary factor (CoF) in the venom of the cobra Naja naja was tested for its behavior in vivo and for its effect on various components of complement in several species of animals and the development of several immunologic reactions. CoF complexed with a plasma protein immediately after injection, the sedimentation rate of the complex being about 9S. The complex which inactivated purified C3 circulated with a half-life of 32 hr in rabbits. High blood levels of the CoF complex and minimal side effects were obtained using multiple injections of CoF over a 24-hr period. Under these conditions hemolytic complement levels fell to less than 10% of normal values in rabbits, rats and guinea pigs. C3 was markedly diminished in these species, and in guinea pigs C3 levels, as revealed in immune adherence, fell to less than 1% of normal. C3 and hemolytic complement levels remained low for 4 to 6 days. In two species tested, C5 protein was also lost during CoF treatment and in rabbits C6 activity diminished about half to one third of normal. The effect of CoF treatment in several immunologic diseases was assayed. Lesions depending upon neutrophil participation for full development were markedly inhibited. In acute nephrotoxic nephritis neutrophil accumulation in glomeruli and proteinuria were diminished. Arthus reactions, especially in the rat, were also inhibited. By contrast, immunologic reactions not requiring neutrophils, i.e., homologous cutaneous anaphylactic reactions in guinea pigs and contact (delayed) sensitivity were not affected by CoF treatment. Other possible effects of CoF in vivo were studied. The numbers of formed elements of the blood were not markedly altered. The most consistent finding was a modest elevation in neutrophils. Hemolysis was avoided by treatment of animals with multiple small doses of CoF. Neutrophils responded normally to immune adherence and chemotactic stimuli. Kininogen levels and clotting tests were unchanged.