SEARCH:   Advanced

Blood, 15 December 2004, Vol. 104, No. 13, pp. 3986-3992. Prepublished online as a Blood First Edition Paper on August 19, 2004; DOI 10.1182/blood-2004-06-2066. This Article Full Text (PDF) All Versions of this Article: 2004-06-2066v1 104/13/3986    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 Eltzschig, H. K Articles by Colgan, S. P Search for Related Content PubMed PubMed Citation Articles by Eltzschig, H. K Articles by Colgan, S. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 3, 2004 Accepted August 7, 2004 Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: Coordination by extracellular nucleotide metabolism Holger K Eltzschig, Linda F Thompson, Jorn Karhausen, Richard J Cotta, Juan C Ibla, Simon C Robson, and Sean P Colgan* Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Anesthesiology, Tubingen University Hospital, Tubingen, Germany Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Department of Anesthesiology Children's Hospital, Harvard Medical School, Boston, MA, USA Transplantation Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA * Corresponding author; email: colgan{at}zeus.bwh.harvard.edu. Hypoxia is a well-documented inflammatory stimulus and results in tissue polymorphonuclear leukocyte (PMN) accumulation. Likewise, increased tissue adenosine levels are commonly associated with hypoxia, and given the anti-inflammatory properties of adenosine, we hypothesized that adenosine production via adenine nucleotide metabolism at the vascular surface triggers an endogenous anti-inflammatory response during hypoxia. Initial in vitro studies indicated that endogenously generated adenosine, through activation of PMN adenosine A2A and A2B receptors, functions as an anti-adhesive signal for PMN binding to microvascular endothelia. Intravascular nucleotides released by inflammatory cells undergo phosphohydrolysis via hypoxia-induced CD39 ecto-apyrase (CD39 converts ATP or ADP to AMP) and CD73 ecto-nucleotidase (CD73 converts AMP to adenosine). Extensions of our in vitro findings using cd39- and cd73-null animals revealed that extracellular adenosine produced through adenine nucleotide metabolism during hypoxia is a potent anti-inflammatory signal for PMN in vivo. These findings identify CD39 and CD73 as critical control points for endogenous adenosine generation and implicate this pathway as an innate mechanism to attenuate excessive tissue PMN accumulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Ohta, A. Ohta, M. Madasu, R. Kini, M. Subramanian, N. Goel, and M. Sitkovsky A2A Adenosine Receptor May Allow Expansion of T Cells Lacking Effector Functions in Extracellular Adenosine-Rich Microenvironments J. Immunol., November 1, 2009; 183(9): 5487 - 5493. [Abstract] [Full Text] [PDF] T. Eckle, M. Koeppen, and H. K. Eltzschig Role of Extracellular Adenosine in Acute Lung Injury Physiology, October 1, 2009; 24(5): 298 - 306. [Abstract] [Full Text] [PDF] M. Katebi, M. Soleimani, and B. N. Cronstein Adenosine A2A receptors play an active role in mouse bone marrow-derived mesenchymal stem cell development J. Leukoc. Biol., March 1, 2009; 85(3): 438 - 444. [Abstract] [Full Text] [PDF] J. Reutershan, I. Vollmer, S. Stark, R. Wagner, K.-C. Ngamsri, and H. K. Eltzschig Adenosine and inflammation: CD39 and CD73 are critical mediators in LPS-induced PMN trafficking into the lungs FASEB J, February 1, 2009; 23(2): 473 - 482. [Abstract] [Full Text] [PDF] H. K. Eltzschig, D. Kohler, T. Eckle, T. Kong, S. C. Robson, and S. P. Colgan Central role of Sp1-regulated CD39 in hypoxia/ischemia protection Blood, January 1, 2009; 113(1): 224 - 232. [Abstract] [Full Text] [PDF] T. Hasegawa, D. Bouis, H. Liao, S. H. Visovatti, and D. J. Pinsky Ecto-5' Nucleotidase (CD73)-Mediated Adenosine Generation and Signaling in Murine Cardiac Allograft Vasculopathy Circ. Res., December 5, 2008; 103(12): 1410 - 1421. [Abstract] [Full Text] [PDF] B. Csoka, L. Himer, Z. Selmeczy, E. S. Vizi, P. Pacher, C. Ledent, E. A. Deitch, Z. Spolarics, Z. H. Nemeth, and G. Hasko Adenosine A2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function FASEB J, October 1, 2008; 22(10): 3491 - 3499. [Abstract] [Full Text] [PDF] M. V. Sitkovsky, J. Kjaergaard, D. Lukashev, and A. Ohta Hypoxia-Adenosinergic Immunosuppression: Tumor Protection by T Regulatory Cells and Cancerous Tissue Hypoxia Clin. Cancer Res., October 1, 2008; 14(19): 5947 - 5952. [Abstract] [Full Text] [PDF] T. Eckle, L. Fullbier, A. Grenz, and H. K. Eltzschig Usefulness of pressure-controlled ventilation at high inspiratory pressures to induce acute lung injury in mice Am J Physiol Lung Cell Mol Physiol, October 1, 2008; 295(4): L718 - L724. [Abstract] [Full Text] [PDF] M. L. Hart, M. Henn, D. Kohler, D. Kloor, M. Mittelbronn, I. C. Gorzolla, G. L. Stahl, and H. K. Eltzschig Role of extracellular nucleotide phosphohydrolysis in intestinal ischemia-reperfusion injury FASEB J, August 1, 2008; 22(8): 2784 - 2797. [Abstract] [Full Text] [PDF] T. Eckle, D. Kohler, R. Lehmann, K. C. El Kasmi, and H. K. Eltzschig Hypoxia-Inducible Factor-1 Is Central to Cardioprotection: A New Paradigm for Ischemic Preconditioning Circulation, July 8, 2008; 118(2): 166 - 175. [Abstract] [Full Text] [PDF] J. C. Morote-Garcia, P. Rosenberger, J. Kuhlicke, and H. K. Eltzschig HIF-1-dependent repression of adenosine kinase attenuates hypoxia-induced vascular leak Blood, June 15, 2008; 111(12): 5571 - 5580. [Abstract] [Full Text] [PDF] M. Takedachi, D. Qu, Y. Ebisuno, H. Oohara, M. L. Joachims, S. T. McGee, E. Maeda, R. P. McEver, T. Tanaka, M. Miyasaka, et al. CD73-Generated Adenosine Restricts Lymphocyte Migration into Draining Lymph Nodes J. Immunol., May 1, 2008; 180(9): 6288 - 6296. [Abstract] [Full Text] [PDF] N. A. Louis, A. M. Robinson, C. F. MacManus, J. Karhausen, M. Scully, and S. P. Colgan Control of IFN-{alpha}A by CD73: Implications for Mucosal Inflammation J. Immunol., March 15, 2008; 180(6): 4246 - 4255. [Abstract] [Full Text] [PDF] G. Hasko and P. Pacher A2A receptors in inflammation and injury: lessons learned from transgenic animals J. Leukoc. Biol., March 1, 2008; 83(3): 447 - 455. [Abstract] [Full Text] [PDF] T. Eckle, M. Faigle, A. Grenz, S. Laucher, L. F. Thompson, and H. K. Eltzschig A2B adenosine receptor dampens hypoxia-induced vascular leak Blood, February 15, 2008; 111(4): 2024 - 2035. [Abstract] [Full Text] [PDF] S. Jalkanen and M. Salmi VAP-1 and CD73, Endothelial Cell Surface Enzymes in Leukocyte Extravasation Arterioscler Thromb Vasc Biol, January 1, 2008; 28(1): 18 - 26. [Abstract] [Full Text] [PDF] D. Kohler, T. Eckle, M. Faigle, A. Grenz, M. Mittelbronn, S. Laucher, M. L. Hart, S. C. Robson, C. E. Muller, and H. K. Eltzschig CD39/Ectonucleoside Triphosphate Diphosphohydrolase 1 Provides Myocardial Protection During Cardiac Ischemia/Reperfusion Injury Circulation, October 16, 2007; 116(16): 1784 - 1794. [Abstract] [Full Text] [PDF] A. Grenz, H. Zhang, M. Hermes, T. Eckle, K. Klingel, D. Y. Huang, C. E. Muller, S. C. Robson, H. Osswald, and H. K. Eltzschig Contribution of E-NTPDase1 (CD39) to renal protection from ischemia-reperfusion injury FASEB J, September 1, 2007; 21(11): 2863 - 2873. [Abstract] [Full Text] [PDF] T. Eckle, L. Fullbier, M. Wehrmann, J. Khoury, M. Mittelbronn, J. Ibla, P. Rosenberger, and H. K. Eltzschig Identification of Ectonucleotidases CD39 and CD73 in Innate Protection during Acute Lung Injury J. Immunol., June 15, 2007; 178(12): 8127 - 8137. [Abstract] [Full Text] [PDF] M. Loffler, J. C. Morote-Garcia, S. A. Eltzschig, I. R. Coe, and H. K. Eltzschig Physiological Roles of Vascular Nucleoside Transporters Arterioscler Thromb Vasc Biol, May 1, 2007; 27(5): 1004 - 1013. [Abstract] [Full Text] [PDF] T. Eckle, T. Krahn, A. Grenz, D. Kohler, M. Mittelbronn, C. Ledent, M. A. Jacobson, H. Osswald, L. F. Thompson, K. Unertl, et al. Cardioprotection by Ecto-5'-Nucleotidase (CD73) and A2B Adenosine Receptors Circulation, March 27, 2007; 115(12): 1581 - 1590. [Abstract] [Full Text] [PDF] A. Grenz, H. Zhang, T. Eckle, M. Mittelbronn, M. Wehrmann, C. Kohle, D. Kloor, L. F. Thompson, H. Osswald, and H. K. Eltzschig Protective Role of Ecto-5'-Nucleotidase (CD73) in Renal Ischemia J. Am. Soc. Nephrol., March 1, 2007; 18(3): 833 - 845. [Abstract] [Full Text] [PDF] N. J. Patel, O. Zaborina, L. Wu, Y. Wang, D. J. Wolfgeher, V. Valuckaite, M. J. Ciancio, J. E. Kohler, O. Shevchenko, S. P. Colgan, et al. Recognition of intestinal epithelial HIF-1{alpha} activation by Pseudomonas aeruginosa Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G134 - G142. [Abstract] [Full Text] [PDF] H. K. Eltzschig, T. Eckle, A. Mager, N. Kuper, C. Karcher, T. Weissmuller, K. Boengler, R. Schulz, S. C. Robson, and S. P. Colgan ATP Release From Activated Neutrophils Occurs via Connexin 43 and Modulates Adenosine-Dependent Endothelial Cell Function Circ. Res., November 10, 2006; 99(10): 1100 - 1108. [Abstract] [Full Text] [PDF] D. Lukashev, B. Klebanov, H. Kojima, A. Grinberg, A. Ohta, L. Berenfeld, R. H. Wenger, A. Ohta, and M. Sitkovsky Cutting Edge: Hypoxia-Inducible Factor 1{alpha} and Its Activation-Inducible Short Isoform I.1 Negatively Regulate Functions of CD4+ and CD8+ T Lymphocytes J. Immunol., October 15, 2006; 177(8): 4962 - 4965. [Abstract] [Full Text] [PDF] H. K. Eltzschig, M. Faigle, S. Knapp, J. Karhausen, J. Ibla, P. Rosenberger, K. C. Odegard, P. C. Laussen, L. F. Thompson, and S. P. Colgan Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26 Blood, September 1, 2006; 108(5): 1602 - 1610. [Abstract] [Full Text] [PDF] A. Zernecke, K. Bidzhekov, B. Ozuyaman, L. Fraemohs, E. A. Liehn, J. M. Luscher-Firzlaff, B. Luscher, J. Schrader, and C. Weber CD73/Ecto-5'-Nucleotidase Protects Against Vascular Inflammation and Neointima Formation Circulation, May 2, 2006; 113(17): 2120 - 2127. [Abstract] [Full Text] [PDF] Z. H. Nemeth, B. Csoka, J. Wilmanski, D. Xu, Q. Lu, C. Ledent, E. A. Deitch, P. Pacher, Z. Spolarics, and G. Hasko Adenosine A2A Receptor Inactivation Increases Survival in Polymicrobial Sepsis J. Immunol., May 1, 2006; 176(9): 5616 - 5626. [Abstract] [Full Text] [PDF] J. B. Volmer, L. F. Thompson, and M. R. Blackburn Ecto-5'-Nucleotidase (CD73)-Mediated Adenosine Production Is Tissue Protective in a Model of Bleomycin-Induced Lung Injury J. Immunol., April 1, 2006; 176(7): 4449 - 4458. [Abstract] [Full Text] [PDF] D. W. Moskowitz, S. Khan, H. K. Eltzschig, J. Karhausen, V. A.J. Kempf, W. M. Nauseef, E. K. Weir, J. Lopez-Barneo, and S. L. Archer Acute oxygen-sensing mechanisms. N. Engl. J. Med., March 2, 2006; 354(9): 975 - 977. [Full Text] [PDF] H. K. Eltzschig, P. Abdulla, E. Hoffman, K. E. Hamilton, D. Daniels, C. Schonfeld, M. Loffler, G. Reyes, M. Duszenko, J. Karhausen, et al. HIF-1-dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia J. Exp. Med., December 5, 2005; 202(11): 1493 - 1505. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020