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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. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-10-054064v1 110/6/1989    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nardi, M. A. Articles by Karpatkin, S. Search for Related Content PubMed PubMed Citation Articles by Nardi, M. A. Articles by Karpatkin, S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Platelet particle formation by anti–GPIIIa49-66 Ab, Ca2+ ionophore A23187, and phorbol myristate acetate is induced by reactive oxygen species and inhibited by dexamethasone blockade of platelet phospholipase A2, 12-lipoxygenase, and NADPH oxidase Michael A. Nardi1, Yelena Gor2, Steven J. Feinmark2, Fang Xu3, and Simon Karpatkin4 1 Department of Pediatrics and 2 Department of Pharmacology, Center for Molecular Therapeutics, Columbia College of Physicians and Surgeons, New York, NY; 3 Department of Anesthesia and 4 Department of Medicine, New York University School of Medicine, New York An HIV antibody (Ab) against platelet integrin GPIIIa49-66 induces complement-independent platelet particle formation by the elaboration of reactive 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 function via the induction of ROS, we examined the effects of the Ca2+ ionophore A23187 [GenBank] 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 this steroid in this unique autoimmune disorder. Dex at therapeutic concentrations inhibited Ab-, A23187 [GenBank] -, 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 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; and (2) platelet PLA2, 12-LO, NADPH oxidase, and cytosol membrane translocation, requirements for ROS production, are inhibited by Dex. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Z. Li, M. A. Nardi, Y.-S. Li, W. Zhang, R. Pan, S. Dang, H. Yee, D. Quartermain, S. Jonas, and S. Karpatkin C-terminal ADAMTS-18 fragment induces oxidative platelet fragmentation, dissolves platelet aggregates, and protects against carotid artery occlusion and cerebral stroke Blood, June 11, 2009; 113(24): 6051 - 6060. [Abstract] [Full Text] [PDF] W. Zhang, M. A. Nardi, W. Borkowsky, Z. Li, and S. Karpatkin Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia Blood, April 23, 2009; 113(17): 4086 - 4093. [Abstract] [Full Text] [PDF] L. Guasti, F. Marino, M. Cosentino, R. C. Maio, E. Rasini, M. Ferrari, L. Castiglioni, C. Klersy, G. Gaudio, A. M. Grandi, et al. Prolonged statin-associated reduction in neutrophil reactive oxygen species and angiotensin II type 1 receptor expression: 1-year follow-up Eur. Heart J., May 1, 2008; 29(9): 1118 - 1126. [Abstract] [Full Text] [PDF]

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