Regulation of the Vascular Barrier during Hypoxia: Role of the 5`-Ectonucleotidase (CD73)

• Applicant: Professor Dr. Peter Rosenberger, since 9/2007
• Subject Area: Anaesthesiology
• Term: from 2004 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5443262

Define the contribution of extracellular nucleotide metabolism via the 5`-Ectonucleotidase(CD73)to vascular permeability in vitro and in vivo. Extracellular nucleotides liberated at inflammatory/hypoxic tissue sites are metabolized to adenosine by surfaceexpressed ectonucleotidases. Ongoing studies indicate that adenosine liberated by this process is available to activate endothelial adenosine receptors, and has been shown to directly regulate endothelial permeabillty. Preliminary studies have defined a critical role for the 5'-ectonucleotidase (CD73) as control point for Generation of extracellular adenosine. Moreover, CD73 is induced by hypoxia, suggesting that a hypoxia adaptive vascular phenotype includes efficient extracellular nucleotide metabolism. Thus, we will pursue work toward: A) Defining details of CD73 function in endothelial permeability in vitro; B) Probing the contribution of CD73 to vascular permeability in vivo. The long-term goals of this work are to elucidate the direct and indirect influences of inflammation on endothelial cell structure and function (particularly endothelial permeability to macromolecules). Results from these experiments will reveal insights into regulation of endothelial permeability and extensions of this work could lead to targets for novel experimental therapeutics.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Professor Holger Klaus Eltzschig, Ph.D., until 8/2007