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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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Submitted March 15, 2005
Accepted June 13, 2005
Platelet NAD(P)H oxidase-generated ROS production regulates IIb 3 integrin activation independent of the NO/cGMP pathway
Antonija J Begonja, Stepan Gambaryan, Jorg Geiger, Barsom Aktas, Miroslava Pozgajova, Bernhard Nieswandt, and Ulrich Walter*
Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Wuerzburg, Germany
Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Wuerzburg, Wuerzburg, Germany
Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Wuerzburg, Germany; Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Wuerzburg, Wuerzburg, Germany
* Corresponding author; email: uwalter{at}klin-biochem.uni-wuerzburg.de.
Platelets play a crucial role in the physiology of primary hemostasis and pathophysiological processes such as arterial thrombosis. Accumulating evidence suggests a role of reactive oxygen species (ROS) in platelet activation. Here we show that platelets activated with different agonists produced intracellular ROS which was reduced by NAD(P)H oxidase inhibitors and superoxide scavengers. In addition, we demonstrate that ROS produced in platelets significantly affected IIb 3 integrin activation but not alpha/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 [DPI (45±9%), apocynin (43±11%)] and superoxide scavengers [tiron (60±9%) and MnTMPyP (70±6)] These inhibitors also reduced platelet aggregation and thrombus formation on collagen under high shear and achieved their effects independent of the NO/cGMP pathway.

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