Influence of endotoxin on arachidonate metabolism in isolated rabbit peritoneum

The serous membranes of the rabbit peritoneal cavity are tissues in which cyclo-oxygenase and lipoxygenase pathways of arachidonate metabolism can be studied simultaneously. After elaboration of the optimum conditions, the metabolism of two concentrations of arachidonic acid (AA) was studied in the presence and absence of endotoxin lipopolysaccharide (LPS) from E. coli O127:B8 (0.1 and 1.0 mg/ml). LPS suppressed the formation of radiolabelled cyclo-oxygenase products (predominantly prostacyclin) at the lower concentration of exogenous AA (0.8 microM), but not at the higher substrate concentration (34.5 microM). The biosynthesis of lipoxygenase metabolites, i.e. monohydroxyeicosatetra-enoic acids (HETEs), was not influenced by LPS. These findings can be explained by an enhanced release of endogenous AA in the prostacyclin forming mesothelial cells in the presence of LPS. Measurements of the endogenous biosynthesis of prostacyclin supported this assumption.