Rouzer C A, Scott W A, Griffith O W, Hamill A L, Cohn Z A
Proc Natl Acad Sci U S A. 1982 Mar;79(5):1621-5. doi: 10.1073/pnas.79.5.1621.
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. Buthionine sulfoximine treatment resulted in inhibition of both prostaglandin E2 and leukotriene C 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 control cells 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, however; increased formation of hydroxyicosatetraenoic acids only partially compensated for the deficit in leukotriene C production. These findings extent our 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 prostaglandin E2 formation.
用谷胱甘肽（GSH）合成抑制剂丁硫氨酸亚砜胺处理小鼠腹腔常驻巨噬细胞，以耗尽细胞内的GSH。通过高效液相色谱法分析了GSH耗尽的巨噬细胞在受到酵母聚糖刺激后释放的花生四烯酸代谢产物。丁硫氨酸亚砜胺处理导致前列腺素E2和白三烯C的合成均受到抑制，这与GSH耗尽的程度直接相关。GSH水平降至正常水平3%的巨噬细胞，其PGE2和LTC的形成分别降至4%和1%。由于前列环素合成增加，以及在较小程度上12-L-羟基-5,8,10-十七碳三烯酸合成增加，GSH缺乏的巨噬细胞分泌的环氧化酶代谢产物总量与对照细胞相同。然而，总的脂氧合酶产物减少；羟基二十碳四烯酸形成的增加仅部分弥补了白三烯C产生的不足。这些发现扩展了我们早期关于GSH耗尽的巨噬细胞中白三烯C合成受抑制的观察结果，并用完整细胞证实了先前提出的GSH在前列腺素E2形成中的作用。
