CHOLESTEROL CRYSTALLIZATION-PROMOTERS IN HUMAN BILE - COMPARATIVE POTENCIES OF IMMUNOGLOBULINS, ALPHA(1)-ACID GLYCOPROTEIN, PHOSPHOLIPASE-C, AND AMINOPEPTIDASE-N

Concanavalin A (Con A)-binding glycoproteins accelerate the rate of ch olesterol crystal formation as a prelude to gallstone formation. Immun oglobulins (IgM, IgA, and IgG), aminopeptidase N (APN), phospholipase C (pcPLC), and alpha1-acid glycoprotein from this Con A fraction have all been proposed as candidate promoters. We immunopurified each of th e six putative promoters and examined their comparative effects by add ing equal amounts to a cholesterol crystal growth assay. The effects o f immunoabsorptive removal of each of the specific candidate promoters from native bile were also compared. In additional studies, the poten cy of these proteins was in the following order: IgM>IgA = AAG>IgG. AP N and pcPLC showed no effect on cholesterol crystal growth at their ap parent physiological concentrations. In subtractive experiments, only a minor loss (<10%) of net promoting activity from that of the whole C on A-bound fraction was observed after immunoabsorptive removal of pcP LC, APN, or immunoglobulins. Total removal of AAG, however, showed a f ar greater loss (@33%) of the net promoting activity. These data indic ate that AAG accounts for the greatest portion of net biliary Con A-bo und promoting activity derived from currently defined and well-identif ied glycoproteins. However, more than 60% of total Con A-binding promo ting activity remains unaccounted for, indicating the presence of othe r important and still unidentified promoters in human bile.