Activated complement and anaphylatoxins increase the in vitro production of prostacyclin by rabbit aorta endothelium.

The effect of activated human serum complement and highly purified anaphylatoxins on the production of prostacyclin (PGI2) by endothelium of the isolated rabbit aorta was investigated. The results indicated that complement activation with endotoxin (LPS) or cobra venom factor (CVF) led to the generation of principles that stimulated PGI2 formation. A similar effect was seen with tryptic cleavage products of complement factors C5 and C3, suggesting the possible involvement of anaphylatoxins. Indeed, on molar base purified porcine C5a and C5a des Arg were at least 1000 times more potent than other vasoactive inflammatory mediators, as stimulators of vascular PGI2 release. Therefore we suggest that complement-mediated stimulation of vascular PGI2 production contributes to the decreased peripheral vascular resistance during endotoxic shock in rabbits. We further propose that C5a-dependent stimulation of PGI2 formation may dilatate resistance vessels, thereby increasing local blood flow. Together with the vascular permeability effects of C5a, this may provide a local regulatory mechanism for histamine- and bradykinin-independent oedema formation during inflammatory reactions.