Platelet NAD(P)H-oxidase-generated ROS production regulates αIIbβ3-integrin activation independent of the NO/cGMP pathway
Platelet NAD(P)H-oxidase-generated ROS production regulates αIIbβ3-integrin activation independent of the NO/cGMP pathway
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DOI：
10.1182/blood-2005-03-1047
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发表时间：
2005-10-15
期刊：
影响因子：
20.3
通讯作者：
Walter, U
中科院分区：
文献类型：
--
作者：
Begonja, AJ;Gambaryan, S;Walter, U
血小板在原发性止血和动脉血栓形成等病理生理过程中起着至关重要的作用。越来越多的证据表明活性氧（ROSs）在血小板活化中的作用。在这里，我们发现被不同激动剂激活的血小板产生细胞内ROSs，被还原性烟酰胺腺嘌呤二核苷酸（磷酸）（NAD(P)H）氧化酶抑制剂和超氧化物清除剂减少。此外，我们证明血小板中产生的Ross显著影响α IIb β 3整合素激活，但不影响α和致密颗粒分泌和血小板形状改变。血小板经NAD(P)H氧化酶抑制剂（二苯碘[DPI][45% +/- 9%]和罗布麻[43% +/- 11%]）和超氧化物清除剂（铁[60% +/- 9%]和Mn（III）四联（1-甲基-4-吡啶基）卟啉[MnTMPyP][70% +/- 6%]）预处理后，凝血酶诱导的整合素α - IIb β 3活化显著降低。这些抑制剂还减少了高剪切下胶原蛋白上的血小板聚集和血栓形成，并且不依赖于一氧化氮/环鸟苷单磷酸（NO/cGMP）途径实现其作用。
Platelets play a crucial role in the physiology of primary hemostasis and pathophysiologic processes such as arterial thrombosis. Accumulating evidence suggests a role of reactive oxygen species (ROSs) in platelet activation. Here we show that platelets activated with different agonists produced intracellular ROSs, which were reduced by reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidase inhibitors and superoxide scavengers. In addition, we demonstrate that Ross produced in platelets significantly affected alpha IIb beta 3 integrin activation but not alpha and dense granule secretion and platelet shape change. Thrombin-induced integrin alpha IIb beta 3 activation was significantly decreased after pretreatment of platelets with NAD(P)H oxidase inhibitors (diphenylene iodonium [DPI] [45% +/- 9%] and apocynin [43% +/- 11%]) and superoxide scavengers (tiron [60% +/- 9%] and Mn(III)tetrakis (1-methyl-4-pyridyl)porphyrin [MnTMPyP] [70% +/- 6%]). These inhibitors also reduced platelet aggregation and thrombus formation on collagen under high shear and achieved their effects independent of the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway.