Abstract
The simultaneous production of prostaglandins, leukotrienes, and hydroxyeicosatetraenoic acids was studied in human peripheral blood monocytes obtained by countercurrent centrifugal elutriation. Monocytes prelabeled for 4 hr with [ 3H]arachidonic acid (AA) released label into the surrounding medium in response to treatment with 12- O-tetradecanoylphorbol-13-acetate (TPA) or calcium ionophore (A23187). High-perfor-mance liquid chromatography of monocyte supernatants demonstrated that labeled compounds included those which eluted with authentic standards for thromboxane B 2, 12- l-hydroxy-5,8,10-heptadecatrienoic acid (HHT), 6-keto-prostaglandin F α, prostaglandin E 2, and 15-hydroxyeicosatetraenoic acid (HETE). 5-HETE and leukotriene B 4 (LtB 4) were detected only in response to ionophore treatment. Highly purified lympho-cytes did not convert AA to autocoids, despite the release of free arachidonate in response to either stimulus. Pretreatment of monocytes with recombinant human interferon (IFN)-γ or IFN-α for 18 hr resulted in enhanced release of labeled arachidonic acid and increased conversion to autocoids after TPA or ionophore stimulation. Absolute amounts of prostaglandin E 2 produced in response to TPA or ionophore treatment were increased as well. These results demonstrate the autocoid profile released by stimulated human monocytes and illustrate the effects of IFN treatment on the production of lipoxygenase metabolites of arachidonic acid as well as cyclooxygenase products.
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