5'-ADENOSINE MONOPHOSPHATE IS THE NEUTROPHIL-DERIVED PARACRINE FACTORTHAT ELICITS CHLORIDE SECRETION FROM T84 INTESTINAL EPITHELIAL-CELL MONOLAYERS

Neutrophil transmigration across intestinal epithelia is thought to co ntribute to epithelial dysfunction and characterizes many inflammatory intestinal diseases. Neutrophils activated by factors, normally prese nt in the lumen, release a neutrophil-derived secretagogue activity to which intestinal epithelia respond with an electrogenic chloride secr etion, the transport event which underlies secretory diarrhea. Using s equential ultrafiltration, column chromatographic, and mass and Raman spectroscopic techniques, neutrophil-derived secretagogue was identifi ed as 5'-AMP. Additional studies suggested that neutrophil-derived 5'- AMP is subsequently converted to adenosine at the epithelial cell surf ace by ecto-5'-nucleotidase and that adenosine subsequently activates intestinal secretion through adenosine receptors on the apical membran e of target intestinal epithelial cells. These findings suggest that t his ATP metabolite may serve as a neutrophil-derived paracrine mediato r that contributes to secretory diarrhea in states of intestinal infla mmation.