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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2024-2035. Prepublished online as a Blood First Edition Paper on December 4, 2007; DOI 10.1182/blood-2007-10-117044. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-10-117044v1 111/4/2024    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 Eckle, T. Articles by Eltzschig, H. K. Search for Related Content PubMed PubMed Citation Articles by Eckle, T. Articles by Eltzschig, H. K. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A2B adenosine receptor dampens hypoxia-induced vascular leak Tobias Eckle1, Marion Faigle1, Almut Grenz2, Stefanie Laucher1, Linda F. Thompson3, and Holger K. Eltzschig1,4 1 Departments of Anesthesiology and Intensive Care Medicine and 2 Pharmacology and Toxicology, Tübingen University Hospital, Tübingen, Germany; 3 Immunobiology and Cancer Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City; and 4 Mucosal Inflammation Program, Department of Anesthesiology and Perioperative Medicine, University of Colorado Health Sciences Center, Denver Extracellular adenosine has been implicated in adaptation to hypoxia and previous studies demonstrated a central role in vascular responses. Here, we examined the contribution of individual adenosine receptors (ARs: A1AR/A2AAR/A2BAR/A3AR) to vascular leak induced by hypoxia. Initial profiling studies revealed that siRNA-mediated repression of the A2BAR selectively increased endothelial leak in response to hypoxia in vitro. In parallel, vascular permeability was significantly increased in vascular organs of A2BAR–/–-mice subjected to ambient hypoxia (8% oxygen, 4 hours; eg, lung: 2.1 ± 0.12-fold increase). By contrast, hypoxia-induced vascular leak was not accentuated in A1AR–/–-, A2AAR–/–-, or A3AR–/–-deficient mice, suggesting a degree of specificity for the A2BAR. Further studies in wild type mice revealed that the selective A2BAR antagonist PSB1115 resulted in profound increases in hypoxia-associated vascular leakage while A2BAR agonist (BAY60-6583 [2-[6-amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)-. phenyl]pyridin-2-ylsulfanyl]acetamide]) treatment was associated with almost complete reversal of hypoxia-induced vascular leakage (eg, lung: 2.0 ± 0.21-fold reduction). Studies in bone marrow chimeric A2BAR mice suggested a predominant role of vascular A2BARs in this response, while hypoxia-associated increases in tissue neutrophils were, at least in part, mediated by A2BAR expressing hematopoietic cells. Taken together, these studies provide pharmacologic and genetic evidence for vascular A2BAR signaling as central control point of hypoxia-associated vascular leak. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Zhou, A. Mohsenin, E. Morschl, H. W. J. Young, J. 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