A NEW SUBGROUP OF LECTIN-BOUND BILIARY PROTEINS BINDS TO CHOLESTEROL CRYSTALS, MODIFIES CRYSTAL MORPHOLOGY, AND INHIBITS CHOLESTEROL CRYSTALLIZATION

Biliary proteins inhibiting or promoting cholesterol crystallization a re assumed to play a major role in cholesterol gallstone pathogenesis. We now report a new group of biliary proteins that bind to cholestero l crystals, modify crystal morphology, and inhibit cholesterol crystal lization. Various glycoprotein mixtures were extracted from abnormal h uman gallbladder bile using lectin affinity chromatography on concanav alin A, lentil, and Helix pomatia columns and were added to supersatur ated model bile, Independent of the protein mixtures added, from the c holesterol 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), re spectively. cholesterol crystallization known so far, Evidence that th e inhibiting effect on cholesterol crystallization is mediated via pro tein-crystal interaction was further provided from scanning electron m icroscopy studies, Crystals grown in presence of inhibiting proteins s howed significantly more ordered structures. Incidence of triclinic cr ystals and regular aggregates was shifted from 30 to 70% compared with controls, These observations may have important implications for unde rstanding the role of biliary proteins in cholesterol crystallization and gallstone pathogenesis.