HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hart, M. L. Articles by Eltzschig, H. K. Search for Related Content PubMed PubMed Citation Articles by Hart, M. L. Articles by Eltzschig, H. K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene

Cutting Edge: A2B Adenosine Receptor Signaling Provides Potent Protection during Intestinal Ischemia/Reperfusion Injury¹

Melanie L. Hart^*, Barbara Jacobi^*, Jens Schittenhelm, Martina Henn^* and Holger K. Eltzschig^2,*,

^* Department of Anesthesiology and Intensive Care Medicine, Center for Inflammation and Hypoxia and Institute of Brain Research, University of Tübingen, Tübingen, Germany; and Mucosal Inflammation Program, Department of Anesthesiology, University of Colorado, Aurora, CO 80045

Gastrointestinal ischemia/reperfusion (IR) injury significantly contributes to the morbidity and mortality of critical illness. In this study, we hypothesized a protective role for extracellular adenosine signaling in intestinal IR injury. Initial profiling studies of mucosal scrapings following murine IR demonstrated selective induction of the A2B adenosine receptor (A2BAR) transcript. Moreover, gene-targeted mice for the A2BAR showed more profound intestinal IR injury compared with controls. In contrast, A2AAR^–/– mice exhibited no differences in intestinal injury compared with littermate controls. In addition, selective inhibition of the A2BAR resulted in enhanced intestinal inflammation and injury during IR. Furthermore, A2BAR agonist treatment (BAY 60-6583) protected from intestinal injury, inflammation, and permeability dysfunction in wild-type mice, whereas the therapeutic effects of BAY 60-6583 were abolished following targeted A2BAR gene deletion. Taken together, these studies demonstrate the A2BAR as a novel therapeutic target for protection during gastrointestinal IR injury.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was funded in part by Fortune Grant F1211269 and European Society of Anaesthesiology Grant D3008762 (both to M.L.H. and H.K.E.).

² Address correspondence and reprint requests to Dr. Holger K. Eltzschig, Associate Professor of Anesthesiology, Mucosal Inflammation Program, Department of Anesthesiology, University of Colorado Denver, 12700 East 19th Avenue, Mailstop B112, Research Complex 2, Room 7124, Aurora, CO 80045. E-mail address: holger.eltzschig{at}ucdenver.edu

³ Abbreviations used in this paper: IR, ischemia/reperfusion; AR, adenosine receptor; AST, aspartate aminotransferase; ALT, alanine aminotransferase; MPO, myeloperoxidase; WT, wild type.

⁴ The online version of this article contains supplemental material.

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]