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Blood, 1 July 2004, Vol. 104, No. 1, pp. 270-280. Prepublished online as a Blood First Edition Paper on March 18, 2004; DOI 10.1182/blood-2003-08-2760. This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 2003-08-2760v1 104/1/270    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 Jison, M. L. Articles by Gladwin, M. T. Search for Related Content PubMed PubMed Citation Articles by Jison, M. L. Articles by Gladwin, M. T. Related Collections Immunobiology Red Cells Cell Cycle Gene Expression Genomics Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease Maria L. Jison, Peter J. Munson, Jennifer J. Barb, Anthony F. Suffredini, Shefali Talwar, Carolea Logun, Nalini Raghavachari, John H. Beigel, James H. Shelhamer, Robert L. Danner, and Mark T. Gladwin From the Critical Care Medicine Department, Warren G. Magnuson Clinical Center; the Mathematical and Statistical Computing Laboratory, Center for Information Technology; the Laboratory of Chemical Biology, National Institute of Diabetes, Digestive and Kidney Diseases; and the Cardiovascular Branch, National Heart, Lung and Blood Institute; National Institutes of Health, Bethesda, MD. In sickle cell disease, deoxygenation of intra-erythrocytic hemoglobin S leads to hemoglobin polymerization, erythrocyte rigidity, hemolysis, and microvascular occlusion. Ischemia-reperfusion injury, plasma hemoglobin-mediated nitric oxide consumption, and free radical generation activate systemic inflammatory responses. To characterize the role of circulating leukocytes in sickle cell pathogenesis we performed global transcriptional analysis of blood mononuclear cells from 27 patients in steady-state sickle cell disease (10 patients treated and 17 patients untreated with hydroxyurea) compared with 13 control subjects. We used gender-specific gene expression to validate human microarray experiments. Patients with sickle cell disease demonstrated differential gene expression of 112 genes involved in heme metabolism, cell-cycle regulation, antioxidant and stress responses, inflammation, and angiogenesis. Inducible heme oxygenase-1 and downstream proteins biliverdin reductase and p21, a cyclin-dependent kinase, were up-regulated, potentially contributing to phenotypic heterogeneity and absence of atherosclerosis in patients with sickle cell disease despite endothelial dysfunction and vascular inflammation. Hydroxyurea therapy did not significantly affect leukocyte gene expression, suggesting that such therapy has limited direct anti-inflammatory activity beyond leukoreduction. Global transcriptional analysis of circulating leukocytes highlights the intense oxidant and inflammatory nature of steady-state sickle cell disease and provides insight into the broad compensatory responses to vascular injury. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. C. Maes, H. M. Schipper, H. M. Chertkow, and E. 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