We recently identified a promoting
glycoprotein in the
concanavalin A-bound fraction of gallbladder bile as a biliary form of alpha 1-glycoprotein (AAG). The concentration of biliary AAG appears to exert an important promoting effect on the speed of
cholesterol nucleation in many patients with
cholesterol gallstone disease. In the current study, we provide information about the biliary concentration of AAG as well as the amount and comparative potency of its subfractions in patients with and without
cholesterol gallstone disease. The amount of total biliary AAG and the amounts of its different
isoforms separated by
concanavalin A affinity chromatography were measured by ELISA. Estimates of absolute concentrations of AAG for each sample were normalized to the sample total
protein content to give relative AAG values. The promoting activity (potency) of immunopurified biliary AAG from
gallstone patients and
gallstone-free controls on
cholesterol crystallization was compared by a crystal growth assay. The mean absolute concentration of AAG in
gallstone-free controls was not significantly different from multiple stone patients. The relative concentration of AAG (micrograms per milligram total
protein) was significantly increased in patients with multiple stones when compared to controls (P < 0.05), and both the absolute and relative concentrations of AAG (micrograms per milligram bile), were three- and to five fold higher in a number of these patients. The functional activity and distribution of AAG in different subfractions was similar in
gallstone patients and
gallstone-free controls. The relative concentration of biliary AAG is significantly greater in
cholesterol gallstone patients with multiple stones than in
gallstone-free controls.(ABSTRACT TRUNCATED AT 250 WORDS)