BACKGROUND: Gallbladder mucin accelerates cholesterol crystal nucleation, an early step in the pathogenesis of gallstones. To examine the role of gallbladder mucin in postnucleation gallstone maturation, the influence of mucin on cholesterol monohydrate crystal growth was studied in a novel model system. METHODS: Cholesterol crystals of a uniform size were incubated in model biles at 37 degrees C with varying cholesterol saturation indices. Crystal size was quantitated by measuring the width and length of individual crystals under polarizing light microscopy and calculating average crystal area. RESULTS: Crystal growth was dependent on the degree of cholesterol supersaturation of bile. Bovine gallbladder mucin (0.5-8 mg/mL) accelerated crystal growth in supersaturated model bile in a concentration- and time-dependent fashion compared with control incubations with bovine serum albumin or model bile alone (P < 0.05). Cholesterol crystal growth was accompanied by a progressive decrease in cholesterol saturation and an increase in total cholesterol crystal mass. Crystal growth was also accompanied by a decrease in total crystal number, suggesting net transfer of cholesterol to larger crystals. CONCLUSIONS: The acceleration of cholesterol crystal growth by gallbladder mucin may be of pathophysiological importance in the postnucleation maturation of cholesterol gallstones.
BACKGROUND: Gallbladder mucin accelerates cholesterol crystal nucleation, an early step in the pathogenesis of gallstones. To examine the role of gallbladder mucin in postnucleation gallstone maturation, the influence of mucin on cholesterol monohydrate crystal growth was studied in a novel model system. METHODS:Cholesterol crystals of a uniform size were incubated in model biles at 37 degrees C with varying cholesterol saturation indices. Crystal size was quantitated by measuring the width and length of individual crystals under polarizing light microscopy and calculating average crystal area. RESULTS: Crystal growth was dependent on the degree of cholesterol supersaturation of bile. Bovine gallbladder mucin (0.5-8 mg/mL) accelerated crystal growth in supersaturated model bile in a concentration- and time-dependent fashion compared with control incubations with bovine serum albumin or model bile alone (P < 0.05). Cholesterol crystal growth was accompanied by a progressive decrease in cholesterol saturation and an increase in total cholesterol crystal mass. Crystal growth was also accompanied by a decrease in total crystal number, suggesting net transfer of cholesterol to larger crystals. CONCLUSIONS: The acceleration of cholesterol crystal growth by gallbladder mucin may be of pathophysiological importance in the postnucleation maturation of cholesterol gallstones.
Authors: Kirk J Maurer; Varada P Rao; Zhongming Ge; Arlin B Rogers; Trisha J Oura; Martin C Carey; James G Fox Journal: Gastroenterology Date: 2007-10 Impact factor: 22.682