BILIARY SECRETORY IMMUNOGLOBULIN-A IS A MAJOR CONSTITUENT OF THE NEW GROUP OF CHOLESTEROL CRYSTAL-BINDING PROTEINS

Background & Aims: Recently we described a new group of lectin-bound b iliary proteins that bind to cholesterol crystals, modify crystal morp hology, and inhibit cholesterol crystallization. The aim of the curren t study was to characterize and identify individual members of this gr oup of cholesterol crystal-binding proteins, Methods: Crystal-binding proteins were purified from human gallbladder bile by lectin affinity chromatography and preparative gel electrophoresis, Purified crystal-b inding proteins were characterized by using cholesterol crystal-growth assays, immunoblotting, and amino acid analysis. For comparison, iden tified biliary proteins were isolated from gallbladder bile by lectin affinity and immunoaffinity chromatography, Results: The individual cr ystal-binding proteins with molecular weights of 74, 63, and 28 kiloda ltons inhibited cholesterol crystallization in a dose-dependent manner (2.5-10 mu g/mL). Immunoblotting with specific antibodies and N-termi nal amino acid sequences revealed that the 74-kilodalton crystal-bindi ng protein is the secretory component, the 63-kilodalton protein is th e heavy chain, and the 28-kilodalton protein is the light chain of hum an secretory immunoglobulin (Ig) A. Isolated biliary IgA showed a pote nt inhibitory effect on cholesterol crystallization in model bile even at levels less than physiological concentrations (1-100 mu g/mL). Con clusions: Biliary secretory IgA is a major constituent of the previous ly described group of cholesterol crystal-binding proteins. Crystal-bi nding IgA may be an important modulator of crystal agglomeration into stones and stone growth in vivo.