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Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2002-11-3624. This Article Full Text (PDF) All Versions of this Article: 2002-11-3624v1 102/13/4472    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 Gomez, G. Articles by Sitkovsky, M. V Search for Related Content PubMed PubMed Citation Articles by Gomez, G. Articles by Sitkovsky, M. V Social Bookmarking                   What's this? Submitted December 2, 2002 Accepted August 19, 2003 Differential requirement for A2a and A3 adenosine receptors for the protective effect of inosine in vivo Gregorio Gomez and Michail V Sitkovsky* Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; Molecular Inflammation Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA * Corresponding author; email: msitkovsky{at}niaid.nih.gov. Inosine is an endogenous nucleoside with immunosuppressive properties that is known to inhibit the accumulation of pro-inflammatory cytokines and protect mice from endotoxin-induced inflammation and lung tissue damage. There are no known receptors specific for inosine, but A3 adenosine receptors (A3R) have been shown to bind inosine resulting in mast cell degranulation and increased vascular permeability. The present study specifically addresses the requirement for A2aR and/or A3R for the protective effect of inosine in two experimental in vivo models of inflammatory disease. The data show that A3R is essential for protection against ConA-induced fulminant hepatitis since only A3R-expressing mice were protected by inosine while wild type and A2aR-deficient mice exhibited severe liver damage even after administration of inosine. In addition, we show in a model of LPS-induced endotoxemia that inosine protected both A2aR-/- and A3R-/- mice from inflammation, but not A2aA3R-double null mice indicating that in this model both A2aR and A3R were employed by inosine. Thus, we demonstrate that A2a and A3 adenosine receptors are differentially utilized by inosine for the down-regulation of tissue damage under different inflammatory conditions in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Ryzhov, R. Zaynagetdinov, A. E. Goldstein, S. V. Novitskiy, M. R. Blackburn, I. Biaggioni, and I. Feoktistov Effect of A2B Adenosine Receptor Gene Ablation on Adenosine-Dependent Regulation of Proinflammatory Cytokines J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 694 - 700. [Abstract] [Full Text] [PDF] J. J. Kobie, P. R. Shah, L. Yang, J. A. Rebhahn, D. J. Fowell, and T. R. Mosmann T Regulatory and Primed Uncommitted CD4 T Cells Express CD73, Which Suppresses Effector CD4 T Cells by Converting 5'-Adenosine Monophosphate to Adenosine J. Immunol., November 15, 2006; 177(10): 6780 - 6786. [Abstract] [Full Text] [PDF] O. Levy, M. Coughlin, B. N. Cronstein, R. M. Roy, A. Desai, and M. R. Wessels The Adenosine System Selectively Inhibits TLR-Mediated TNF-{alpha} Production in the Human Newborn J. Immunol., August 1, 2006; 177(3): 1956 - 1966. [Abstract] [Full Text] [PDF] R. Guinzberg, D. Cortes, A. Diaz-Cruz, H. Riveros-Rosas, R. Villalobos-Molina, and E. Pina Inosine released after hypoxia activates hepatic glucose liberation through A3 adenosine receptors Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E940 - E951. [Abstract] [Full Text] [PDF] A. Fortin, D. Harbour, M. Fernandes, P. Borgeat, and S. Bourgoin Differential expression of adenosine receptors in human neutrophils: up-regulation by specific Th1 cytokines and lipopolysaccharide J. Leukoc. Biol., March 1, 2006; 79(3): 574 - 585. [Abstract] [Full Text] [PDF] H. Shen, G.-J. Chen, B. K. Harvey, P. C. Bickford, and Y. Wang Inosine Reduces Ischemic Brain Injury in Rats Stroke, March 1, 2005; 36(3): 654 - 659. [Abstract] [Full Text] [PDF] S. Buckley, L. Barsky, K. Weinberg, and D. Warburton In vivo inosine protects alveolar epithelial type 2 cells against hyperoxia-induced DNA damage through MAP kinase signaling Am J Physiol Lung Cell Mol Physiol, March 1, 2005; 288(3): L569 - L575. [Abstract] [Full Text] [PDF]

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