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Blood, 15 October 2005, Vol. 106, No. 8, pp. 2757-2760.
Prepublished online as a Blood First Edition Paper on June 23, 2005; DOI 10.1182/blood-2005-03-1047.
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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief report
Platelet NAD(P)H-oxidasegenerated ROS production regulates IIb 3-integrin activation independent of the NO/cGMP pathway
Antonija Jurak Begonja,
Stepan Gambaryan,
Jörg Geiger,
Barsom Aktas,
Miroslava Pozgajova,
Bernhard Nieswandt, and
Ulrich Walter
From the Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg; and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Würzburg, Germany.
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 IIb 3 integrin activation but not alpha and dense granule secretion and platelet shape change. Thrombin-induced integrin IIb 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.

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