Lauri D, Cerletti C, de Gaetano G
J Lab Clin Med. 1985 Jun;105(6):653-8.
The irreversible human platelet aggregation induced by threshold concentrations of platelet-activating factor (PAF) in citrated plasma was reversed by aspirin (100 mumol/L, with 10 minutes' preincubation). The aspirin-sensitive amplification was linked to thromboxane generation, although thromboxane could be successfully replaced by cyclic endoperoxides, as suggested by the lack of effect of dazoxiben, a selective thromboxane-synthase inhibitor. The inhibitory effect of aspirin could be overcome by using 10 times higher PAF concentrations or, even more effectively, by combining threshold concentrations of both PAF and one of the other agonists studied (ADP, epinephrine, and U-46619, a stable endoperoxide analog, but not serotonin). The irreversible response obtained in both experimental conditions could also be made reversible by the use of BW 755C or nordihydroguaiaretic acid, inhibitors of both cyclooxygenase and lipoxygenase. It is concluded that the aspirin-sensitive pathway is sufficient but not necessary to amplify the primary response of human platelets to PAF. These data may be relevant to the current debate on the efficacy of aspirin in thrombosis prevention.
在枸橼酸盐血浆中，血小板活化因子（PAF）的阈浓度所诱导的不可逆性人血小板聚集，可被阿司匹林（100 μmol/L，预孵育10分钟）逆转。阿司匹林敏感的放大作用与血栓素生成有关，尽管如选择性血栓素合酶抑制剂达唑氧苯无效所提示的那样，血栓素可被环内过氧化物成功替代。使用高10倍的PAF浓度，或者更有效地，通过将PAF的阈浓度与所研究的其他激动剂之一（ADP、肾上腺素以及U-46619，一种稳定的内过氧化物类似物，但不是5-羟色胺）联合使用，可克服阿司匹林的抑制作用。在两种实验条件下所获得的不可逆反应，也可通过使用环氧化酶和脂氧化酶的抑制剂BW 755C或去甲二氢愈创木酸而变得可逆。得出的结论是，阿司匹林敏感途径对于放大人类血小板对PAF的初级反应而言是充分的，但并非必要的。这些数据可能与当前关于阿司匹林在预防血栓形成方面疗效的争论相关。
