[Role of biliary proteins in pathogenesis of cholesterol gallstones]

Cholelithiasis is a frequent disease in developed countries with significant economical implications. While the multifactorial pathogenesis of cholesterol gallstones has been widely accepted, the relative importance of the various contributing factors is not yet clear. One focus of research in recent years has been the identification and functional analysis of biliary proteins. Few proteins are synthesized in the biliary tract itself, the majority reflect the composition of serum proteins. Many biliary proteins modify cholesterol crystallization, the initial step of cholesterol gallstone formation. In cholelithiasis, biliary concentration of many pronucleating proteins are increased. However, this may be a consequence rather than the cause of the disease, because a majority of these proteins are acute-phase reactants. They may be secreted into bile at increased concentrations because of--often asymptomatic--cholecystitis due to gallstone disease. A number of protein-lipid interactions have been observed in search of a mechanism of action of biliary effector proteins. Only recently the potential modification of lipid removal from gallbladder bile by Apo A-I was described in addition to its direct antinucleating effect. In conclusion, biliary proteins directly modify cholesterol crystallization by protein-lipid interactions and may influence lipid absorption from the gallbladder.