THE EFFECT OF LYSOLECITHIN ON PROSTANOID AND PLATELET-ACTIVATING-FACTOR FORMATION BY HUMAN GALLBLADDER MUCOSAL CELLS

IT has been demonstrated that lysolecithin (lysophosphatidyl choline, LPC) produces experimental cholecystitis in cats mediated by arachidon ic acid metabolites. LPC is a cytolytic agent that has been postulated as a contributing factor in the development of cholecystitis in human s. The purpose of this research was to evaluate the effect of LPC on h uman gall-bladder mucosal cell phospholipase A(2) and cyclooxygenase a ctivity. Gall-bladder mucosal cells were isolated from the gall-bladde rs of patients undergoing routine cholecystectomy. Fresh, isolated cel ls were maintained in tissue culture and stimulated with varying doses of LPC. Platelet-activating factor concentration was quantitated as a n index of phospholipase A(2) activity and prostanoids were measured a s an index of cyclooxygenase activity. Also, the effect of LPC on cycl ooxygenase 1 and 2 expression in microsomal protein was evaluated. LPC caused dose related increases in 6-keto-PGF(1 alpha) and PAF produced by human gall-bladder mucosal cells. Exposure of human gall-bladder m ucosal cells to LPC failed to elicit expression of constitutive cycloo xygenase-1, while the expression of inducible cyclooxygenase-2 was inc reased The results of this study indicate that LPC induces the formati on of prostanoids and PAF by human gall-bladder mucosal cells, suggest ing that this substance may promote the development of gall-bladder in flammation.