Sporn P H, Murphy T M, Peters-Golden M
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0360.
J Leukoc Biol. 1990 Jul;48(1):81-8. doi: 10.1002/jlb.48.1.81.
We have previously demonstrated that the biologically important oxidant hydrogen peroxide (H2O2) triggers release and metabolism of arachidonic acid (AA) in the alveolar macrophage (AM). In this study, we evaluated the ability of glucocorticoids to inhibit rat AM AA metabolism stimulated by H2O2, as compared to the particulate zymosan. Methylprednisolone and other glucocorticoids failed to significantly inhibit release of AA stimulated by H2O2, while markedly reducing AA release in response to zymosan. Similarly, methylprednisolone only weakly inhibited synthesis of thromboxane (Tx)B2 stimulated by H2O2, while inhibiting zymosan-induced eicosanoid synthesis to a marked degree. On the other hand, the phospholipase inhibitor mepacrine strongly inhibited AA release and TxB2 formation stimulated by both H2O2 and zymosan, indicating that H2O2 induced AA metabolism is indeed susceptible to pharmacologic inhibition. The failure of glucocorticoids to inhibit AA metabolism stimulated by H2O2 in the AM may in part explain their inability to ameliorate oxidant-mediated lung inflammation and injury.
我们之前已经证明，具有生物学重要意义的氧化剂过氧化氢（H2O2）可引发肺泡巨噬细胞（AM）中花生四烯酸（AA）的释放和代谢。在本研究中，我们评估了糖皮质激素抑制H2O2刺激的大鼠AM中AA代谢的能力，并与颗粒状酵母聚糖进行了比较。甲基强的松龙和其他糖皮质激素未能显著抑制H2O2刺激的AA释放，而能显著减少酵母聚糖刺激引起的AA释放。同样，甲基强的松龙仅微弱抑制H2O2刺激的血栓素（Tx）B2合成，却能显著抑制酵母聚糖诱导的类花生酸合成。另一方面，磷脂酶抑制剂米帕林强烈抑制H2O2和酵母聚糖刺激引起的AA释放和TxB2形成，表明H2O2诱导的AA代谢确实易受药物抑制。糖皮质激素未能抑制AM中H2O2刺激的AA代谢，这可能部分解释了它们无法改善氧化剂介导的肺部炎症和损伤的原因。
