Cobra venom factor, an activator of the complement system, enhances the bowel necrosis induced by platelet-activating factor

Abstract

We have previously produced an experimental model of ischemic bowel necrosis in the rat by injecting platelet activating factor (PAF) (7 μg/kg) into the mesenteric vascular bed. The dose of PAF required to produce necrosis could be reduced to 50% if the animal was pretreated with bacterial endotoxin (lipopolysaccharide) (20 /mgg/rat). The mechanism of this potentiating effect of lipopolysaccharide is nuclear, but activation of the complement system may be one of the contributing factors. To investigate the role of the complement system, we injected cobra venom factor (CVF) (1 unit/kg) to activate the complement system before injection of PAF (2μg/kg) into the superior mesenteric artery. CVF and PAF were also injected separately at the same dosage to other groups of rats. CVF activated the complement system, but by itself did not produce gross necrosis of the bowel. PAF alone caused 3 out of 9 rats treated to develop bowel necrosis. In contrast, combination of the two produced bowel necrosis in all 6 rats thus treated. CVF did not enhance the effects of PAF on hemoconcentration and leukopenia, but aggravated the hypotension caused by PAF. PAF, on the other hand, also enhanced activation of the complement system by CVF. To investigate the specificity of PAF on complement activation, lyso-PAF was used in combination with CVF. It was found that lyso-PAF did not have a significant potentiating effect on CVF-induced complement activation and, by itself, it had no effect on complement activation, blood pressure, white blood cell count or hematocrit. Lyso-PAF, with or without CVF, also failed to produced bowel necrosis. Our results show that: (a) complement activation by itself was not sufficient to cause ischemic bowel necrosis; (b) lyso-PAF was ineffective in causing bowel lesions, while PAF at low doses occasionally induced mild necrotic lesions; (c) PAF enhanced the activation of the complement system by CVF, while lyso-PAF was ineffective; and (d) CVF (which activates complement) potentiated the effect of PAF, to cause bowel necrosis.