An appraisal of the role of biliary phospholipases in the pathogenesis of gallstone disease

Human bile contains proteins that influence nucleation of cholesterol. Recently, it has been suggested that activity of phospholipases in bile may play a role in this process. To study the influence of phospholipase on nucleation we have determined the effect of phospholipases A2, C and D on the nucleation time of model bile. Phospholipase C decreased the nucleation time, whereas phospholipase A2 inhibited nucleation. The phospholipases were effective only at relatively high concentrations. Phospholipase D was strongly inhibited in model bile and probably only influenced the nucleation time by an aspecific protein effect. The cleavage products of the different phospholipases were determined in native bile samples of 14 cholesterol gallstone patients, 6 patients without stones and 4 patients with pigment stones. In all samples, choline, phosphorylcholine and free fatty acids (FFA) could be detected. However, there was no significant difference between the three groups of patients. The rate of production of choline, phosphorylcholine and FFA was measured in bile incubated at 37 degrees C. Again, there was no significant difference between the three groups of patients. We conclude that phospholipase activity in bile does not play an important role in the pathogenesis of gallstone disease.