MODULATION OF CELLULAR PHOSPHOLIPID FATTY-ACIDS AND LEUKOTRIENE-B4 SYNTHESIS IN THE HUMAN INTESTINAL-CELL (CACO-2)

The ability of a human colonocyte epithelial cell line (CaCo-2) to synthesise leukotriene B4 was examined. In addition, the effects of stimulation with calcium ionophore, inhibition by a drug which specifically prevents activation of 5-lipoxygenase, and modification of the fatty acid composition of membrane phospholipids on leukotriene B4 synthesis were assessed. Incubation with calcium ionophore (A23187) resulted in a dose and time dependent increase in leukotriene B4 synthesis. After cell phospholipids had been enriched with oleic acid, linoleic acid, and arachidonic acid, leukotriene B4 synthesis was found to be increased 3.2-fold, 5.5-fold, and 6.1-fold above control. Treatment with MK-886 inhibited leukotriene B4 synthesis by 79% to 94% in the various groups. Variations in the polyunsaturated fatty acid content of intestinal epithelial cells could be important in the modulation of cellular responses. We have shown for the first time in this human intestinal epithelial cell its ability to synthesise leukotriene B4. In addition, leukotriene B4 synthesis can be modulated by the fatty acid composition of membrane phospholipids, which can be altered by dietary fatty acids. The synthesis of chemotactic factors, such as leukotriene B4, by the mucosal epithelium may contribute to the recruitment of granulocytes into the colonic mucosa and across the epithelium, giving rise to the crypt abscesses which characterise ulcerative colitis.