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Blood, 15 January 2006, Vol. 107, No. 2, pp. 558-565. Prepublished online as a Blood First Edition Paper on September 15, 2005; DOI 10.1182/blood-2005-05-2152. This Article Full Text (PDF) All Versions of this Article: 2005-05-2152v1 107/2/558    most recent Alert me when this article is cited Alert me if a correction is posted 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 Wang, J.-G. Articles by Slungaard, A. Search for Related Content PubMed PubMed Citation Articles by Wang, J.-G. Articles by Slungaard, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 31, 2005 Accepted September 6, 2005 The principal eosinophil peroxidase product, HOSCN,is a uniquely potent phagocyte oxidant inducer of endothelial cell tissue factor activity: a potential mechanism for thrombosis in eosinophilic inflammatory states Jian-Guo Wang, Shawn Mahmud, Jake A Thompson, Jian-Guo Geng, Nigel S Key, and Arne Slungaard* Department of Medicine, Hematology, Oncology, and Transplantation Section and the Vascular Biology Center, University of Minnesota, Minneapolis, MN, USA * Corresponding author; email: slung001{at}umn.edu. In vivo, bromide (Br-), nitrite (NO2-), and thiocyanate (SCN-) compete for oxidation by eosinophil peroxidase (EPO) and H2O2 yielding, respectively, HOBr, NO2, and HOSCN. We have recently shown that SCN- is the strongly preferred substrate for EPO in vivo and that HOSCN, in contrast to other EPO-generated oxidants and HOCl, is a relatively weak, cell-permeant, sulfhydryl (SH)-reactive oxidant. We here show that HOSCN is a uniquely potent (up to 100-fold) phagocyte oxidant inducer of tissue factor (TF) activity in human umbilical vein endothelial cells (HUVEC). This induction is attributable to transcriptional upregulation of TF gene expression dependent upon both activation of the p65/c-Rel TF-kB transcription factor and activity of the ERK 1/2 kinase pathway upstream of Egr-1 and was markedly further enhanced in the presence of wortmannin, an inhibitor of the PI3 kinase/Akt pathway. HOSCN also markedly activates the proinflammatory p65/p50 NF-kB pathway. Based on these findings we hypothesize that HOSCN generated by adherent and infiltrating eosinophils may provoke the development of a prothrombotic and proinflammatory endothelial/endocardial phenotype that promotes the pronounced thrombotic diathesis characteristic of the Hypereosinophilic Syndrome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. Chen, M. Bacanamwo, and D. G. Harrison Activation of p300 Histone Acetyltransferase Activity Is an Early Endothelial Response to Laminar Shear Stress and Is Essential for Stimulation of Endothelial Nitric-oxide Synthase mRNA Transcription J. Biol. Chem., June 13, 2008; 283(24): 16293 - 16298. [Abstract] [Full Text] [PDF] J. Wang, S. A. Mahmud, P. B. Bitterman, Y. Huo, and A. Slungaard Histone Deacetylase Inhibitors Suppress TF-{kappa}B-dependent Agonist-driven Tissue Factor Expression in Endothelial Cells and Monocytes J. Biol. Chem., September 28, 2007; 282(39): 28408 - 28418. [Abstract] [Full Text] [PDF] C. D. Campbell and D. A. S. Marshall A case of Budd-Chiari Syndrome presenting in a lady with newly diagnosed Churg-Strauss Syndrome Rheumatology, May 1, 2007; 46(5): 890 - 890. [Full Text] [PDF] J.-G. Wang, S. A. Mahmud, J. Nguyen, and A. Slungaard Thiocyanate-Dependent Induction of Endothelial Cell Adhesion Molecule Expression by Phagocyte Peroxidases: A Novel HOSCN-Specific Oxidant Mechanism to Amplify Inflammation J. Immunol., December 15, 2006; 177(12): 8714 - 8722. [Abstract] [Full Text] [PDF]

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