Schleimer R P, Davidson D A, Lichtenstein L M, Adkinson N F
J Immunol. 1986 Apr 15;136(8):3006-11.
The effects of antiinflammatory steroids on arachidonic acid metabolite release from human lung fragments were analyzed. Incubation of lung fragments for 24 hr with 10(-6) M dexamethasone inhibited the net release of the prostacyclin metabolite 6-keto-PGF1 alpha, PGE2, and PGF2 alpha from lung fragments stimulated with anti-IgE but failed to inhibit the anti-IgE-induced release of PGD2, TXB2, and iLTC4. The IC50 of dexamethasone for inhibition of both spontaneous and anti-IgE-induced 6-keto-PGF1 alpha release was approximately 2 X 10(-8) M, and a 6-hr preincubation with the drug was required for 50% inhibition of prostaglandin release. Other agents were tested for activity in stimulating arachidonic acid metabolite release from human lung fragments. FMLP (fmet-leu-phe) stimulated the release of all metabolites tested (6-keto-PGF1 alpha, PGD2, PGE2, PGF2 alpha, TXB2, iLTC4); platelet-activating factor (PAF), but not lysoPAF, stimulated the release of PGD2, TXB2, and iLTC4. In contrast to the case with anti-IgE, where dexamethasone failed to inhibit net PGD2 and TXB2 release, the steroid inhibited the release of these metabolites stimulated by both FMLP and PAF. The steroid inhibited iLTC4 release induced by the highest concentration of PAF (10(-6)M) but did not inhibit iLTC4 release stimulated by either 10(-7) M PAF, FMLP, or anti-IgE. Because neither FMLP nor PAF caused the release of PGD2 or TXB2 from purified human lung mast cells, and because they also failed to induce histamine release from lung fragments, it is suggested that these stimuli produce PGD2 and TXB2 release in lung fragments through an action on a cell distinct from the mast cell. This suggestion is supported by the selective inhibition of the release of these arachidonic acid metabolites by dexamethasone. We suggest that the inhibitory action of steroids on arachidonic acid metabolite in human lung fragments contributes to their therapeutic efficacy in pulmonary diseases.
分析了抗炎类固醇对人肺组织碎片中花生四烯酸代谢产物释放的影响。用10⁻⁶ M地塞米松孵育人肺组织碎片24小时，可抑制抗IgE刺激的肺组织碎片中前列环素代谢产物6-酮-PGF1α、PGE2和PGF2α的净释放，但未能抑制抗IgE诱导的PGD2、TXB2和白三烯C4（iLTC4）的释放。地塞米松抑制自发和抗IgE诱导的6-酮-PGF1α释放的半数抑制浓度（IC50）约为2×10⁻⁸ M，且药物预孵育6小时才能抑制50%的前列腺素释放。测试了其他药物刺激人肺组织碎片中花生四烯酸代谢产物释放的活性。甲酰甲硫氨酰-亮氨酰-苯丙氨酸（FMLP）刺激了所有测试代谢产物（6-酮-PGF1α、PGD2、PGE2、PGF2α、TXB2、iLTC4）的释放；血小板活化因子（PAF）而非溶血PAF刺激了PGD2、TXB2和iLTC4的释放。与抗IgE的情况不同，地塞米松未能抑制PGD2和TXB2的净释放，而该类固醇抑制了FMLP和PAF刺激的这些代谢产物的释放。该类固醇抑制了最高浓度（10⁻⁶ M）PAF诱导的iLTC4释放，但未抑制10⁻⁷ M PAF、FMLP或抗IgE刺激的iLTC4释放。由于FMLP和PAF均未从纯化的人肺肥大细胞中引起PGD2或TXB2的释放，且它们也未能诱导肺组织碎片中组胺的释放，因此提示这些刺激通过作用于不同于肥大细胞的细胞在肺组织碎片中产生PGD2和TXB2的释放。地塞米松对这些花生四烯酸代谢产物释放的选择性抑制支持了这一推测。我们认为类固醇对人肺组织碎片中花生四烯酸代谢产物的抑制作用有助于其在肺部疾病中的治疗效果。
