Complement derived factors and prostacyclin formation by rabbit isolated peritoneum and cultured mesothelial cells

Activation of rabbit or human serum complement led to the generation of factors which stimulated prostacyclin biosynthesis by isolated rabbit peritoneal tissue. Their formation was proportional to the degree of complement activation, measured as consumption of total hemolytic activity or immunoreactive C3. The stimulation of prostacyclin biosynthesis was mimicked by fragments obtained by trypsinisation of C3 (C3f) and C5 (C5f). Peritoneal macrophages, which could stimulate peritoneal prostacyclin biosynthesis through release of chemical mediators in response to C3f or C5f, were not essential, since the C3f and C5f also stimulated prostacyclin biosynthesis in monolayers of cultured mesothelial cells. Of the putative mediators, platelet activating factor (PAF) was inactive as a stimulator of peritoneal PGI2 biosynthesis. The finding that activated complement components stimulate prostacyclin biosynthesis forms an explanation for the endotoxin-induced rise in rabbit arterial blood levels of prostacyclin and may have wider implications for the understanding of inflammatory reactions.