COMPARISON OF THE INDUCTION OF CYCLOOXYGENASE AND NITRIC-OXIDE SYNTHASE BY ENDOTOXIN IN ENDOTHELIAL-CELLS AND MACROPHAGES

Endotoxin causes the expression of inducible nitric oxide (NO) synthas e and cyclooxygenase-2. We have compared the ability of endotoxin to i ncrease the activities of these enzymes in bovine aortic endothelial c ells and the macrophage cell line (J774.2). Endotoxin (1 mu g ml(-1); for 24 h) caused a time-dependent increase in the accumulation of cycl ooxygenase metabolites from endogenous arachidonic acid, in both cell types. Cyclooxygenase activity towards exogenous arachidonic acid (30 mu M; for 15 min) was also increased in both cell types. Endothelial c ells and macrophages also contained comparable amounts of cyclooxygena se-2 protein after incubation with endotoxin for 24 h which was preven ted by pretreatment with cycloheximide (10 mu g ml(-1); 30 min prior t o endotoxin). Endotoxin for 24 h caused a time-dependent increase in n itrite accumulation in macrophages, but not in endothelial cells. Thus , endotoxin increased cyclooxygenase activity and induced cyclooxygena se-2 protein in endothelial cells and macrophages. Endotoxin also incr eased NO synthase activity in macrophages, but not in endothelial cell s.