PLATELET-ACTIVATING-FACTOR ACETYLHYDROLASES IN CACO-2 CELLS AND EPITHELIUM OF NORMAL AND ULCERATIVE-COLITIS PATIENTS

Background & Aims: Platelet-activating factor (PAF) is a potent inflammatory mediator implicated in the pathogenesis of inflammatory bowel disease and necrotizing enterocolitis, Metabolism by platelet-activating factor acetylhydrolase (PAF-AH) is the major pathway for platelet-activating factor degradation. The aim of this study was to investigate the possible role of intestinal epithelium as a source of PAF-AH, Methods: Intracellular and secreted PAF-AHs were characterized in human colonic epithelial cells isolated from histologically normal mucosa and inflamed mucosa from patients with ulcerative colitis and in the human intestinal epithelial cell line Caco-2 by measuring the metabolism of [H-3]PAF to [H-3]lysoPAF. Results: Human colonic epithelial cells and Caco-2 cells synthesize and secrete PAF-AH as shown by in vitro hydrolysis of [H-3]PAF to [H-3]lysoPAF in cell lysates and conditioned media, Both intracellular and secreted PAF-AHs are calcium-independent and substrate-specific for phospholipids similar to PAF, Epithelial cells from involved areas of resections for ulcerative colitis had increased levels of secreted PAF-AH and decreased levels of intracellular PAF-AH compared with epithelial cells from histologically normal areas. Conclusions: Human colonic epithelial cells and Caco-2 cells produce intracellular and secreted PAF-AHs, which are distinct proteins. This is the first demonstration of PAF-AH production by epithelial cells.