Carcino embryonic antigen-related cell adhesion molecule 1 is the 85-kilodalton pronase-resistant biliary glycoprotein in the cholesterol crystallization promoting low density protein-lipid complex

A pronase resistant 85-kd glycoprotein in the Concanavalin A-binding fracti on (CABF) of biliary glycoproteins has been reported to act as a promotor o f cholesterol crystallization. De Bruijn et al. (Gastroenterology 1996;110: 1936-1944) found this protein in a low-density protein-lipid complex (LDP) with potent cholesterol crystallization promoting activity. This study iden tifies and characterizes this protein. An LDP was prepared from CABF by dis continuous gradient ultracentrifugation. Proteins were analyzed by sodium d odecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), blotting and immunochemical staining with anti-carcinoembryonic antigen, CEA-related adh esion molecule 1 (CEACAM1) cross-reacting antibodies. Biliary concentration s of CEA cross-reacting proteins were determined in patients with and witho ut gallstones. Two isoforms of CEACAM1 (85- and 115-kd bands), CEA and 2 CE A crossreacting protein bands of 40 and 50 kd were found in human bile. All bands were also present in CABF, but only a subfraction of the 85-kd band found in the LDP was resistant to digestion with pronase. CEACAM1-85 exhibi ted potent cholesterol crystallization promoting activity in vitro and acco unted for most of the activity in CABF. Total CEA cross-reacting protein co ncentrations were the same in gallbladder biles from patients with choleste rol and pigment gallstones but only half of those in biles from nongallston e subjects. In conclusion, we have identified the protein component of the cholesterol crystallization promoting LDP to be CEACAM1-85.