1 Prostanoid synthesis was induced in bone marrow-derived macrophages by addition of exogenous arachidonic acid to the cell cultures. When the cells were preincubated with dexamethasone (10'-and 10 6m) overnight, prostaglandin synthesis was inhibited by 66.5 + 2.8% and 56.7 + 2.9% (mean + s.d.; n = 3) respectively. 2 Endogenous membrane bound phospholipase A2 was measured with labelled phospholipids used as substrates. The enzyme activity with phosphatidylcholine and phosphatidylethanolamine as substrates was inhibited by 27.0 + 8.3% and 23.3 + 11.1% (n = 4) respectively, in dexamethasonetreated macrophages compared to control cells. Neither the distribution of radiolabelled arachidonic acid among the different phospholipid species nor the release of arachidonic acid from prelabelled cells were significantly impaired by pretreatment of the macrophages with dexamethasone (1 gM).3 The enzyme activity of the cyclo-oxygenase/prostaglandin E (PGE) isomerase was measured in cell membranes from control cells and dexamethasone-treated cells. It was inhibited by 40.0 + 8.4% (n = 4) in dexamethasone-treated cells as compared to control cells. Thus, glucocorticoids inhibit not only phospholipase A2 in these cells, but predominantly inhibit arachidonic acid metabolism subsequent to its release from phospholipids.

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Mononuclear phagocytes convert arachidonic acid and other unsaturated fatty acids from intracellular sources to a variety of oxygenated metabolites such as prostaglandins and leukotrienes which are secreted into the surrounding medium. Other oxidative products such as hydroxylinoleic acids are reacylated into cellular constituents. The underlying metabolic pathways are activated by numerous stimuli of exogenous or endogenous origin. Depending on the state of activation and cell differentiation, the organ of origin and the nature of the stimulus used, macrophages elaborate a distinct spectrum of oxidative arachidonic acid metabolites. The contribution of these metabolites to the proinflammatory properties of macrophages is twofold: As autocrine signals they modulate the synthesis of diverse macrophage products and they influence cellular functions of other cells such as T-lymphocytes.

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