title: Mucins and calcium phosphate precipitates additively stimulate cholesterol crystallization.
abstract: Human biliary mucin and calcium binding protein (CBP) influence formation of both calcium salt precipitates and cholesterol crystals and colocalize in the center of cholesterol gallstones. We investigated how physiological concentrations of these proteins regulate cholesterol crystallization in model biles, supersaturated with cholesterol and calcium salts, mimicking pathological human bile. Using polarizing light microscopy and nephelometry to assess cholesterol crystallization, the influence of calcium ions and calcium phosphate precipitates in the absence and presence of mucin, CBP, and human serum albumin was determined. Calcium phosphate precipitates stimulated cholesterol crystallization more strongly than soluble calcium. Mucin also stimulated, and with soluble calcium or calcium phosphate precipitates additively increased, the cholesterol crystal mass. In the absence of mucin, only human serum albumin plus CBP, not these proteins individually, decreased the stimulating effect of calcium phosphate precipitates but not of soluble calcium. However, seeding of calcium phosphate precipitates in biles with mucins resulted in near complete cholesterol crystallization within one day whether CBP and HSA were or were not also present. In conclusion, calcium salt precipitates plus human biliary mucins induce rapid and complete crystallization of cholesterol from model biles, little influenced by human biliary calcium binding proteins.
authors.affiliation: Department of Gastrointestinal and Liver Diseases, Academic Medical Center at the University of Amsterdam, The Netherlands.
authors.forename: A A
authors.initials: AA
authors.lastname: van den Berg
authors.forename: J D
authors.initials: JD
authors.lastname: van Buul
authors.forename: G N
authors.initials: GN
authors.lastname: Tytgat
authors.forename: A K
authors.initials: AK
authors.lastname: Groen
authors.forename: J D
authors.initials: JD
authors.lastname: Ostrow
mesh_terms: D001646:Bile / Q000737:chemistry; D002130:Calcium Phosphates / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D011232:Chemical Precipitation; D002769:Cholelithiasis / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry*; D003460:Crystallization; D006801:Humans; D007700:Kinetics; D008859:Microscopy, Polarization; D008954:Models, Biological; D009077:Mucins / Q000494:pharmacology*; D009391:Nephelometry and Turbidimetry; D012709:Serum Albumin / Q000494:pharmacology
chemical_list: D002130:Calcium Phosphates; D002135:Calcium-Binding Proteins; D009077:Mucins; D012709:Serum Albumin; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; D002784:Cholesterol; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous