The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 25 August 2003 doi:10.1084/jem.20030891
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 543K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Eltzschig, H. K.
Right arrow Articles by Colgan, S. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Eltzschig, H. K.
Right arrow Articles by Colgan, S. P.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© Rockefeller University Press, 0022-1007/2003/9/783 $5.00
The Journal of Experimental Medicine, Volume 198, Number 5, 783-796

Coordinated Adenine Nucleotide Phosphohydrolysis and Nucleoside Signaling in Posthypoxic Endothelium : Role of Ectonucleotidases and Adenosine A2B Receptors



Holger K. Eltzschig1,7, Juan C. Ibla2, Glenn T. Furuta3, Martin O. Leonard4, Kenneth A. Jacobson5, Keiichi Enjyoji6, Simon C. Robson6 and Sean P. Colgan1

1 Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital
2 Department of Anesthesiology, Perioperative and Pain Medicine
3 Combined Program for Pediatric Gastroenterology and Nutrition, Children's Hospital, Harvard Medical School, Boston, MA 02115
4 The Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
5 Molecular Recognition Section, National Institutes of Health, Bethesda, MD 20892
6 Transplantation Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115
7 Department of Anesthesiology and Intensive Care Medicine, Eberhard-Karls-University, D-72076 Tübingen, Germany

Address correspondence to Sean P. Colgan, Ph.D., Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Thorn Building 704, 75 Francis St., Boston, MA 02115. Phone: (617) 278-0599 ext. 1401; Fax: (617) 278-6957; email: colgan{at}zeus.bwh.harvard.edu

Limited oxygen delivery to tissues (hypoxia) is common in a variety of disease states. A number of parallels exist between hypoxia and acute inflammation, including the observation that both influence vascular permeability. As such, we compared the functional influence of activated polymorphonuclear leukocytes (PMN) on normoxic and posthypoxic endothelial cells. Initial studies indicated that activated PMN preferentially promote endothelial barrier function in posthypoxic endothelial cells (>60% increase over normoxia). Extension of these findings identified at least one soluble mediator as extracellular adenosine triphosphate (ATP). Subsequent studies revealed that ATP is coordinately hydrolyzed to adenosine at the endothelial cell surface by hypoxia-induced CD39 and CD73 (>20-and >12-fold increase in mRNA, respectively). Studies in vitro and in cd39-null mice identified these surface ecto-enzymes as critical control points for posthypoxia-associated protection of vascular permeability. Furthermore, insight gained through microarray analysis revealed that the adenosine A2B receptor (AdoRA2B) is selectively up-regulated by hypoxia (>5-fold increase in mRNA), and that AdoRA2B antagonists effectively neutralize ATP-mediated changes in posthypoxic endothelial permeability. Taken together, these results demonstrate transcription coordination of adenine nucleotide and nucleoside signaling at the vascular interface during hypoxia.

Key Words: adenosine • ectonucleotidase • endothelium • neutrophil • inflammation


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS