Biochemical mechanisms of generation of bradykinin by endotoxin

The vasodilatory properties of bradykinin are compatible with a pathogenetic role in man and subhuman primates during endotoxemia. The peptide is generated during endotoxemia when peripheral vascular resistance is decreased. A number of mechanisms of kinin generation can be recruited by endotoxin. In plasma containing complement and 19S antibody to endotoxin, the polysaccharide moiety of endotoxin activates plasma kallikreins. Similar quantities of bradykinin are generated in all species tested. Therefore, species-related variation in production of the peptide in vivo depends on the interaction of endotoxin with other tissues. Granulocytes of primates (as opposed to those of rabbits) contain a cytoplasmic kallikrein or kallikrein activator. Granulocytes release their cytoplasmic enzymes (and presumably kallikreins) when phagocytizing endotoxin. In-vitro phagocytosis requires complement and lipid-rich endotoxin. Polysaccharide fractions of endotoxin do not produce effects on granulocytes, their kinin generation, or the cardiovascular system. We suggest that differences in endotoxin effect among species are largely related to effects of the lipid moiety of endotoxin and the chemical machinery of the cells this moiety penetrates.