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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-oxidase–generated ROS production regulates {alpha}IIb{beta}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 {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.


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