Objective. Cholesterol phospholipid vesicles play an important role in the nucleation of cholesterol in bile. Recent studies have identified an additional vesicle population in human bile. In this study, the role of these small vesicles as cholesterol carriers was examined. Methods. Gallbladder bile was obtained from 60 patients at cholecystectomy. Large vesicles, small vesicles, lamellae, and mixed micelles were separated using gel filtration chromatography. Results. Small vesicles were present in bile from the majority of patients both with and without cholesterol gallstones, whereas the void volume vesicle fraction was found almost exclusively in bile from patients with cholesterol gallstones. Both large vesicular and small vesicular cholesterol increased as total bile cholesterol concentration increased; however, the cholesterol-phospholipid ratio in the large vesicle fraction from patients with cholesterol stones was significantly greater than the ratio in small vesicles (1.6 ± 0.3 vs. 1.0 ≤ 0.1, p < 0.05). Whole bile cholesterol crystal appearance time was correlated significantly with the percentage of cholesterol transported by large vesicles (r = 0.63, p < 0.001) but not with the percentage of cholesterol present in small vesicles. Finally, large vesicles isolated by gel filtration chromatography formed cholesterol crystals faster than small vesicles (5.3 ± 2 vs. 17.4 ± 4 days, p < 0.01). Conclusions. These data suggest that a heterogenous population of vesicles is present in human gallbladder bile. As bile becomes saturated with cholesterol, it increasingly is solubilized by both small and large vesicles. The small vesicles have relatively less cholesterol and are more stable than the larger variety, from which cholesterol is most likely to precipitate.
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