CHARACTERIZATION OF A SMALL VESICULAR CHOLESTEROL CARRIER IN HUMAN GALLBLADDER BILE

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 rol e oi these small vesicles as cholesterol carriers was examined. Method s Gallbladder bile was obtained from 60 patients at cholecystectomy. L arge vesicles, small vesicles, lamellae, and mixed micelles were separ ated using gel filtration chromatography. Results Small vesicles were present in bile from the majority of patients both with and without ch olesterol gallstones, whereas the void volume vesicle fraction was fou nd almost exclusively in bile from patients with cholesterol gallstone s. Both large vesicular and small vesicular cholesterol increased as t otal bile cholesterol concentration increased; however, the cholestero l-phospholipid ratio in the large vesicle fraction from patients with cholesterol stones was significantly greater than the ratio in small v esicles (1.6 +/- 0.3 vs. 1.0 less than or equal to 0.1, p < 0.05). Who le bile cholesterol crystal appearance time was correlated significant ly 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 sug gest that a heterogenous population of vesicles is present in human ga llbladder bile. As bile becomes saturated with cholesterol, it increas ingly is solubilized by both small and large vesicles. The small vesic les have relatively less cholesterol and are more stable than the larg er variety, from which cholesterol is most likely to precipitate.