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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 6, 2005 Accepted November 14, 2005 Red blood cells express a functional endothelial nitric oxide synthase Petra Kleinbongard, Rainer Schulz, Tienush Rassaf, Thomas Lauer, Andre Dejam, Thomas Jax, Intan Kumara, Putrika Gharini, Svetlana Kabanova, Burcin Oezueyaman, Hans-Georg Schnurch, Axel Godecke, Artur-Aron Weber, Mirko Robenek, Horst Robenek, Wilhelm Bloch, Peter Rosen, and Malte Kelm* Department of Medicine, Medical Clinic I, University Hospital RTWH Aachen, Aachen, Germany Institute of Pathophysiology, Medical School, University of Essen, Essen, Germany Department of Medicine, Division of Cardiology, Pulmonary Diseases and Angiology, Heinrich-Heine-University, Duesseldorf, Germany Department of Gynaecology and Obstetrics, Lukas Hospital, Neuss, Germany Department of Cardiovascular Physiology, Heinrich-Heine-University, Duesseldorf, Germany Department of Pharmacology, Heinrich-Heine-University, Duesseldorf, Germany Department of Cell Biology and Ultrastructure Research, Leibniz-Institute of Artheriosclerosis Research, Munster, Germany Department of Molecular and Cellular Sport Medicine, Sport University Cologne, Cologne, Germany Department of Clinical Biochemistry, German Diabetes Research Institute, Heinrich-Heine-University, Duesseldorf, Germany * Corresponding author; email: kelm{at}uni-duesseldorf.de. The synthesis of nitric oxide (NO) in the circulation has been attributed exclusively to the vascular endothelium. Red blood cells (RBC) have been demonstrated to carry a non-functional NO synthase (NOS) and, due to their huge hemoglobin content, have been assumed to metabolize large quantities of NO. More recently, however, RBC have been identified to reversibly bind, transport, and release NO within the cardiovascular system. We now provide evidence that RBC from humans express an active and functional endothelial type NOS (eNOS), which is localized in the plasma membrane and the cytoplasm of RBC. 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 RBC is comparable to that of cultured human endothelial cells. RBC in eNOS-/- mice in contrast to wild-type mice lack NOS protein and activity strengthening the evidence of an eNOS in RBC. These data show an eNOS like protein and activity in RBC serving regulatory functions in RBC 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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