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Blood, 15 September 2007, Vol. 110, No. 6, pp. 1989-1996.
Prepublished online as a Blood First Edition Paper on June 1, 2007; DOI 10.1182/blood-2006-10-054064.
 Previous Article | Next Article 
Submitted October 26, 2006
Accepted May 29, 2007
Platelet particle formation by anti-GPIIIa49-66 Ab, Ca2+ lonophore A23187 and phorbol myristate acetate (PMA) is induced by reactive oxygen species and inhibited by dexamethasone blockade of platelet phospholipase A2 (PLA2), 12-lipoxygenase(12-LO)
and NADPH Oxidase
Michael A Nardi, Yelena Gor, Steven J Feinmark, Fang Xu, and Simon Karpatkin*
Department of Pediatrics, New York University School of Medicine, New York, NY, United States
Department of Pharmacology, Center for Molecular Therapeutics, Columbia College of Physicians and Surgeons, New York, NY, United States
Department of Anesthesia, New York University School of Medicine, New York, NY, United States
Department of Medicine, New York University School of Medicine, New York, NY, United States
* Corresponding author; email: simon.karpatkin{at}med.nyu.edu.
An HIV Ab against platelet integrin GPIIIa49-66 induces complement independent platelet formation by the elaboration of reaction oxygen species (ROS) downstream of the activation of the platelet NADPH oxidase by the 12-lipoxygenase (12-LO) product, 12(S)HETE. To determine whether other inducers of platelet particle formation also fuction via the induction of ROS, we examined the effects of the Ca2+ ionophore, A23187 and phorbol myristate acetate (PMA). Both agents induced oxidative platelet particle formation in an identical fashion as Ab, requiring Ca2+ flux, and 12(S) HETE production as well as intact NADPH oxidase and 12-LO pathways. Since HIV-ITP patients with this Ab correct their platelet counts with Dexamethasone (Dex) we examined the role of Dex in this unique autoimmune disorder. Dex at therapeutic concentrations inhibited Ab, A23187 or PMA-induced platelet particle formation by inhibiting platelet PLA2, 12-LO and NADPH oxidase. The operational requirement of translocation of PLA2, 12-LO and NADPH oxidase components (p67 phox) from cytosol to membrane for induction of reactive oxygen species (ROS) was both inhibited and partially reversed by Dex in platelets. We conclude that: 1) Platelet particle formation can be induced by the generation of ROS. 2) Platelet PLA2, 12-LO, NADPH oxidase and cytosol membrane translocation requirements for ROS production, are inhibited by Dex.
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