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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2943-2951. Prepublished online as a Blood First Edition Paper on December 20, 2005; DOI 10.1182/blood-2005-10-3992. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-10-3992v1 107/7/2943    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 Kleinbongard, P. Articles by Kelm, M. Search for Related Content PubMed PubMed Citation Articles by Kleinbongard, P. Articles by Kelm, M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Red Cells Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Red blood cells express a functional endothelial nitric oxide synthase Petra Kleinbongard, Rainer Schulz, Tienush Rassaf, Thomas Lauer, André Dejam, Thomas Jax, Intan Kumara, Putrika Gharini, Svetlana Kabanova, Burcin Özüyaman, Hans-Georg Schnürch, Axel Gödecke, Artur-A. Weber, Mirko Robenek, Horst Robenek, Wilhelm Bloch, Peter Rösen, and Malte Kelm From the Department of Medicine, Medical Clinic I, University Hospital Rheinisch-Westfälische-Technische-Hochschule-Aachen (RTWH), Aachen; Department of Medicine, Division of Cardiology, Pulmonary Diseases and Angiology, Heinrich-Heine-University, Düsseldorf; Departments of Cardiovascular Physiology and Pharmacology, Heinrich-Heine-University, Düsseldorf; Department of Clinical Biochemistry, German Diabetes Research Institute, Heinrich-Heine-University, Düsseldorf; Department of Gynecology and Obstetrics, Lukas Hospital, Neuss; Institute of Pathophysiology, Medical School, University of Essen; Department of Cell Biology and Ultrastructure Research, Leibniz-Institute of Artheriosclerosis Research, Münster; and Department of Molecular and Cellular Sport Medicine, Sport University Cologne, Germany. The synthesis of nitric oxide (NO) in the circulation has been attributed exclusively to the vascular endothelium. Red blood cells (RBCs) have been demonstrated to carry a nonfunctional NO synthase (NOS) and, due to their huge hemoglobin content, have been assumed to metabolize large quantities of NO. More recently, however, RBCs have been identified to reversibly bind, transport, and release NO within the cardiovascular system. We now provide evidence that RBCs from humans express an active and functional endothelial-type NOS (eNOS), which is localized in the plasma membrane and the cytoplasm of RBCs. This NOS is regulated by its substrate L-arginine, by calcium, and by phosphorylation via PI3 kinase. RBC-NOS activity regulates deformability of RBC membrane and inhibits activation of platelets. The NOS-dependent conversion of L-arginine in RBCs is comparable to that of cultured human endothelial cells. RBCs in eNOS-/- mice in contrast to wild-type mice lack NOS protein and activity, strengthening the evidence of an eNOS in RBCs. These data show an eNOS-like protein and activity in RBCs serving regulatory functions in RBCs and platelets, which may stimulate new approaches in the treatment of NO deficiency states inherent to several vascular and hematologic diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Does eNOS stand for erythrocytic NO synthase? Mark T. Gladwin Blood 2006 107: 2595-2596. [Full Text] [PDF] This article has been cited by other articles: F. B. Jensen The dual roles of red blood cells in tissue oxygen delivery: oxygen carriers and regulators of local blood flow J. Exp. Biol., November 1, 2009; 212(21): 3387 - 3393. [Abstract] [Full Text] [PDF] D. Mihov, J. Vogel, M. Gassmann, and A. 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