Functional coupling of cyclooxygenase 1 and 2 to discrete prostanoid synthases in liver macrophages

The profile of released prostanoids after addition of exogenous arachidonic acid to resident liver macrophages is different from the profile obtained in lipopolysaccharide-pretreated cells. In resident and lipopolysaccharide- pretreated cells, AA leads to a release of thromboxane B-2, prostaglandin F -2 alpha, E-2, and D-2. A specifically enhanced formation of prostaglandin E-2 is obtained in lipopolysaccharide-pretreated cells. Resident liver macr ophages express cyclooxygenase 1, and thromboxane A(2)-, prostaglandin F-2 alpha-, E-2-, and D-2-synthase. Treatment with lipopolysaccharide induces-i n addition to cyclooxygenase 2-an enhanced expression of the prostaglandin E-2 synthase. In resident liver macrophages, the formation of prostanoids f rom exogenous arachidonic acid is completely inhibited by SC560 (a specific inhibitor of cyclooxygenase 1), but remains unchanged with SC236 (a specif ic inhibitor of cyclooxygenase 2). In lipopolysaccharide-pretreated liver m acrophages, the formation of thromboxane B-2, prostaglandin F-2 alpha and D -2 is equally inhibited by SC560 and SC236 by about 50%. In contrast, the f ormation of prostaglandin E-2 is inhibited to a greater extent by SC560 (75 %) compared to SC236 (26%). We conclude from these data, that in lipopolysa ccharide-pretreated Liver macrophages (i) cyclooxygenase 1 and 2 couple bot h to discrete prostanoid synthases, (ii) the functional coupling of cycloox ygenase 1 and 2 to the thromboxane A(2)-, prostaglandin F-2 alpha-, and D-2 -synthase is almost identical, and (iii) the enhanced prostaglandin E-2 syn thesis is due to an enhanced expression of the prostaglandin E-2 synthase, which is coupled more efficiently to cyclooxygenase 1. (C) 2000 Academic Pr ess.