A new subgroup of lectin-bound biliary proteins binds to cholesterol crystals, modifies crystal morphology, and inhibits cholesterol crystallization

被引:28
作者
Busch, N
Lammert, F
Marschall, HU
Matern, S
机构
[1] Department of Internal Medicine III, Aachen University of Technology
关键词
gallstone; cholesterol crystallization; bile; inhibitor; biliary proteins;
D O I
10.1172/JCI118374
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Biliary proteins inhibiting or promoting cholesterol crystallization are assumed to play a major role in cholesterol gallstone pathogenesis. We now report a new group of biliary proteins that bind to cholesterol crystals, modify crystal morphology, and inhibit cholesterol crystallization. Various glycoprotein mixtures were extracted from abnormal human gallbladder bile using lectin affinity chromatography on concanavalin A, lentil, and Helix pomatia columns and were added to supersaturated model bile, Independent of the protein mixtures added, from the cholesterol crystals harvested, the same four GPs were isolated having molecular masses of 16, 28, 63, and 74 kD, respectively, Each protein was purified using preparative SDS-PAGE, and influence on cholesterol crystallization in model bile was tested at 10 mu g/ml. Crystal growth was reduced by 76% (GP63), 65% (GP16), 55% (GP74), and 40% (GP28), respectively. cholesterol crystallization known so far, Evidence that the inhibiting effect on cholesterol crystallization is mediated via protein-crystal interaction was further provided from scanning electron microscopy studies, Crystals grown in presence of inhibiting proteins showed significantly more ordered structures. Incidence of triclinic crystals and regular aggregates was shifted from 30 to 70% compared with controls, These observations may have important implications for understanding the role of biliary proteins in cholesterol crystallization and gallstone pathogenesis.
引用
收藏
页码:3009 / 3015
页数:7
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