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Prepublished online as a Blood First Edition Paper on January 9, 2003; DOI 10.1182/blood-2002-10-3147. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-10-3147v1 101/10/3877    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 Hadjur, S. Articles by Jirik, F. R. Search for Related Content PubMed PubMed Citation Articles by Hadjur, S. Articles by Jirik, F. R. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Phagocytes Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2003, Vol. 101, No. 10, pp. 3877-3884 HEMATOPOIESIS Increased sensitivity of Fancc-deficient hematopoietic cells to nitric oxide and evidence that this species mediates growth inhibition by cytokines Suzana Hadjur and Frank R. Jirik From the Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada. Fanconi anemia complementation group C (Fancc)-deficient murine bone marrow progenitors demonstrate increased sensitivity to growth inhibition by interferon  (IFN), tumor necrosis factor  (TNF), and macrophage inflammatory protein 1 (MIP-1). This property has been proposed as a possible pathogenic factor in the marrow failure seen in Fanconi anemia. Supporting our hypothesis that nitric oxide (NO) production might be a common effector in this sensitivity, we found that cytokine-mediated growth inhibition of Fancc/ bone marrow cells was prevented by inhibiting NO synthase activity. Interestingly, Fancc/ hematopoietic cells also exhibited increased growth inhibition on exposure to 2 distinct NO-generating agents, S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and diethylenetriamine nitric oxide adduct (DETA/NO). In keeping with the sensitivity of Fancc/ cells to IFN, inducible nitric oxide synthase (iNOS) levels and nitrite release were both increased following stimulation of Fancc/ macrophages with this cytokine, either alone or in combination with bacterial lipopolysaccharide. Suggesting a plausible mechanism for the increased expression of iNOS, IFN-stimulated Fancc/ macrophages generated higher levels of phospho-Stat1, a positive regulator of inos (nos2) gene expression. These observations, while confined to C57BL/6 Fancc/ hematopoietic cells, raise the possibility that nitric oxide has a role in the pathogenesis of Fanconi anemia. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Bijangi-Vishehsaraei, M. R. Saadatzadeh, A. Werne, K. A. W. McKenzie, R. Kapur, H. Ichijo, and L. S. Haneline Enhanced TNF-{alpha}-induced apoptosis in Fanconi anemia type C-deficient cells is dependent on apoptosis signal-regulating kinase 1 Blood, December 15, 2005; 106(13): 4124 - 4130. [Abstract] [Full Text] [PDF] S. Franco, H. J. van de Vrugt, P. Fernandez, M. Aracil, F. Arwert, and M. A. Blasco Telomere dynamics in Fancg-deficient mouse and human cells Blood, December 15, 2004; 104(13): 3927 - 3935. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020