EPITHELIAL NEUTROPHIL INTERACTIONS IN IBD

Emory University, Atlanta GA

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Abstract

DESCRIPTION: The goal of this proposal is to understand interactions between intestinal epithelial cells and neutrophils that occurs during intestinal inflammation. An approach has been used with in vitro epithelial monolayers and peripheral blood neutrophils. The specific new aims are to determine the compartment in neutrophils which release 5' AMP and study the biology of the epithelial ectoenzyme CD73 and receptor A2b for adenosine. Second, studies of the role of CD47 in epithelial cell neutrophil interactions will be studied by overexpressing CD47 in epithelial cells and expressing dominant negative mutants. A novel epithelial ligand will be defined, and finally the role of intraepithelial lymphocytes will be defined in a mixed cell culture system. The third aim will be to identify novel factors expressed during bacterial infection of epithelial cells, and finally the ability of long acting analogs of lipoxins to inhibit neutrophil interactions and murine colitis will be studied.