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Blood, 1 September 2006, Vol. 108, No. 5, pp. 1602-1610. Prepublished online as a Blood First Edition Paper on May 2, 2006; DOI 10.1182/blood-2006-02-001016. This Article Full Text (PDF) All Versions of this Article: blood-2006-02-001016v1 108/5/1602    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 Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 3, 2006 Accepted April 24, 2006 Endothelial catabolism of extracellular adenosine during hypoxia: Role of surface adenosine deaminase and CD26 Holger K Eltzschig*, Marion Faigle, Simone Knapp, Jorn Karhausen, Juan Ibla, Peter Rosenberger, Kirsten C Odegard, Peter C Laussen, Linda F Thompson, and Sean P Colgan Department of Anesthesiology and Intensive Care Medicine, Tubingen University Hospital, Germany Department of Anesthesiology,Perioperative & Pain Medicine,Children's Hospital,Harvard Medical S. Center for Experimental Therapeutics & Reperfusion Injury, Brigham and Women's Hospital, Boston, MA Immunobiology & Cancer Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA * Corresponding author; email: heltzschig{at}partners.org. Extracellular levels of adenosine increase during hypoxia. While acute increases in adenosine are important to counter-balance excessive inflammation or vascular leakage, chronically elevated adenosine levels may be toxic. Thus, we reasoned that clearance mechanisms may exist to offset deleterious influences of chronically elevated adenosine. Guided by microarray-results revealing induction of endothelial adenosine deaminase (ADA) mRNA in hypoxia, we utilized in vitro and in vivo models of adenosine signaling, confirming induction of ADA protein and activity. Further studies revealed that the ADA-complexing protein CD26 is coordinately induced by hypoxia, effectively localizing ADA activity at the endothelial cell-surface. Moreover, ADA surface binding was effectively blocked with gp120-treatment, a protein known to specifically compete for ADA-CD26 binding. Functional studies of murine hypoxia revealed inhibition of ADA with deoxycoformycin enhances protective responses mediated by adenosine (vascular leak, neutrophil accumulation). Analysis of plasma ADA activity in pediatric patients with chronic hypoxia undergoing cardiac surgery demonstrated a 4.1± 0.6-fold increase in plasma ADA activity compared to controls. Taken together, these results reveal induction of ADA as innate metabolic adaptation to chronically elevated adenosine levels during hypoxia. In contrast, during acute hypoxia associated with vascular leakage and excessive inflammation, ADA-inhibition may serve as a therapeutic strategy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Ups and downs of adenosine Joel Linden Blood 2006 108: 1430. [Full Text] [PDF] This article has been cited by other articles: 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] 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] 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] D. J. Drucker Dipeptidyl Peptidase-4 Inhibition and the Treatment of Type 2 Diabetes: Preclinical biology and mechanisms of action Diabetes Care, June 1, 2007; 30(6): 1335 - 1343. [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]

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