Regular Article
Functional Coupling of Cyclooxygenase 1 and 2 to Discrete Prostanoid Synthases in Liver Macrophages

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Abstract

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 B2, prostaglandin F, E2, and D2. A specifically enhanced formation of prostaglandin E2 is obtained in lipopolysaccharide-pretreated cells. Resident liver macrophages express cyclooxygenase 1, and thromboxane A2-, prostaglandin F-, E2-, and D2-synthase. Treatment with lipopolysaccharide induces—in addition to cyclooxygenase 2—an enhanced expression of the prostaglandin E2 synthase. In resident liver macrophages, the formation of prostanoids from exogenous arachidonic acid is completely inhibited by SC560 (a specific inhibitor of cyclooxygenase 1), but remains unchanged with SC236 (a specific inhibitor of cyclooxygenase 2). In lipopolysaccharide-pretreated liver macrophages, the formation of thromboxane B2, prostaglandin F and D2 is equally inhibited by SC560 and SC236 by about 50%. In contrast, the formation of prostaglandin E2 is inhibited to a greater extent by SC560 (75%) compared to SC236 (26%). We conclude from these data, that in lipopolysaccharide-pretreated liver macrophages (i) cyclooxygenase 1 and 2 couple both to discrete prostanoid synthases, (ii) the functional coupling of cyclooxygenase 1 and 2 to the thromboxane A2-, prostaglandin F-, and D2-synthase is almost identical, and (iii) the enhanced prostaglandin E2 synthesis is due to an enhanced expression of the prostaglandin E2 synthase, which is coupled more efficiently to cyclooxygenase 1.

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    Abbreviations used: AA, arachidonic acid; COX, cyclooxygenase; LPS, lipopolysaccharide; PG, prostaglandin; cPLA2, cytosolic phospholipase A2; Tx, thromboxane.

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