Arachidonic acid metabolism in glutathione-deficient macrophages.
- 1 March 1982
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 79 (5), 1621-1625
- https://doi.org/10.1073/pnas.79.5.1621
Abstract
Mouse resident peritoneal macrophages were treated with the glutathione (GSH) synthesis inhibitor buthionine sulfoximine to deplete intracellular GSH. The arachidonic acid metabolites released by the GSH-depleted macrophages in response to a zymosan challenge were analyzed by HPLC [high pressure liquid chromatography]. Buthionine sulfoximine treatment resulted in inhibition of both prostaglandin[PG]E2 and leukotriene C [LTC] synthesis that was directly related to the degree of GSH depletion. Macrophages in which GSH levels were reduced to 3% of normal exhibited reductions to 4% and 1%, respectively, in PGE2 and LTC formation. The total quantity of cyclooxygenase metabolites secreted by GSH-deficient macrophages was identical to that of controls as a result of increased synthesis of prostacyclin and, to a lesser extent, 12-L-hydroxy-5,8,10-heptadecatrienoic acid. Total lipoxygenase products were decreased; increased formation of hydroxyicosatetraenoic acids only partially compensated for the deficit in LTC production. These findings extend earlier observations on the inhibition of leukotriene C synthesis in GSH-depleted macrophages and confirm with intact cells the previously suggested role of GSH in PGE2 formation.Keywords
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