Palmer R M, Salmon J A
Biochem Pharmacol. 1985 May 1;34(9):1485-90. doi: 10.1016/0006-2952(85)90688-4.
The effects of aspirin, indomethacin, phenylbutazone, eicosatetraynoic acid (ETYA), nordihydroguaiaretic acid (NDGA) and 3-amino-1-[3-(trifluoromethyl)-phenyl]-2-pyrazoline (BW755C) on human neutrophil degranulation induced by A23187 and F-Met-Leu-Phe (FMLP) have been studied. These effects have been compared with those on A23187 induced leukotriene B4 (LTB4) and thromboxane B2 (TXB2) synthesis by these cells to elucidate the relationship between LTB4 formation and degranulation. All compounds inhibited TXB2 synthesis by 50% at concentrations between 0.0016 and 50 microM. The synthesis of LTB4 was inhibited by 50% by ETYA (1.9 microM) and by NDGA (0.52 microM). Degranulation induced by A23187 and FMLP was inhibited by 50% by ETYA (16 and 11 microM respectively) and by NDGA (1.5 and 6.5 microM respectively). In the case of ETYA the concentrations required to inhibit degranulation were significantly higher than those required to inhibit LTB4 synthesis. In contrast, BW755C inhibited LTB4 synthesis by 50% at 2.8 microM but did not affect A23187-induced degranulation and was only a weak inhibitor of FMLP-induced degranulation (50% inhibition at 89 microM). The effects of the above compounds on the omega-oxidation of LTB4 by human neutrophils has also been studied to investigate the mechanism of action of these compounds. None of the above compounds affected the metabolism of LTB4 by these cells suggesting that their actions are not as non-specific anti-oxidants. These data indicate that human neutrophil degranulation induced by FMLP and A23187 is independent of LTB4 synthesis.
研究了阿司匹林、吲哚美辛、保泰松、二十碳四炔酸（ETYA）、去甲二氢愈创木酸（NDGA）和3-氨基-1-[3-(三氟甲基)-苯基]-2-吡唑啉（BW755C）对A23187和F-甲硫氨酰-亮氨酰-苯丙氨酸（FMLP）诱导的人中性粒细胞脱颗粒的影响。将这些影响与它们对这些细胞由A23187诱导的白三烯B4（LTB4）和血栓素B2（TXB2）合成的影响进行比较，以阐明LTB4形成与脱颗粒之间的关系。所有化合物在0.0016至50微摩尔浓度之间均可使TXB2合成抑制50%。ETYA（1.9微摩尔）和NDGA（0.52微摩尔）可使LTB4合成抑制50%。ETYA（分别为16和11微摩尔）和NDGA（分别为1.5和6.5微摩尔）可使A23187和FMLP诱导的脱颗粒抑制50%。就ETYA而言，抑制脱颗粒所需的浓度显著高于抑制LTB4合成所需的浓度。相比之下，BW755C在2.8微摩尔时可使LTB4合成抑制50%，但不影响A23187诱导的脱颗粒，并且只是FMLP诱导脱颗粒的弱抑制剂（在89微摩尔时抑制50%）。还研究了上述化合物对人中性粒细胞LTB4ω-氧化的影响，以研究这些化合物的作用机制。上述化合物均未影响这些细胞对LTB4的代谢，表明它们的作用并非作为非特异性抗氧化剂。这些数据表明，FMLP和A23187诱导的人中性粒细胞脱颗粒与LTB4合成无关。
