HETEROGENEITY OF HUMAN BILIARY MUCIN - FUNCTIONAL IMPLICATIONS

1. Human gallbladder mucin has been implicated as playing a role in th e pathogenesis of gallstones. In previous studies no differences have been found in the content or composition of mucins derived from contro l bile or cholesterol gallstone bile. Until now, no differences were a lso found between these two groups of mucins with regard to their abil ity to cause cholesterol nucleation. In the accompanying paper we have reported that there is a strong heterogeneity of gallbladder mucins d erived from individual patients (M. J. A. van Wijland, J. H. Klinkspoo r, L. Th. de Wit, R. P. J. Oude Elferink, G. N. J. Tytgat and A. K. Gr oen, Clin Sci 1994; 86: 67-74). In the present study we further invest igated a possible patient to patient heterogeneity of mucin by means o f immunological and functional characterization of mucins isolated fro m hepatic bile of six different patients with gallstones. 2. Considera ble heterogeneity was found. Two of the mucins barely reacted with a p olyclonal anti-mucin antibody, whereas the other four mucins reacted v ery strongly. Lectin-binding studies indicated that the glycans of the se two mucins expressed less D-N-acetylgalactosamine residues than the other four mucins. This was confirmed by analyses of the glycan compo sitions. These studies furthermore indicated that the glycans were of the O-linked type, contained alpha-D-N-acetylglucosamine and were fuco sylated, sialylated and sulphated to different extents. Except for a s trong heterogeneity in the sugar composition of the mucins, heterogene ity was also found in the biological activity of the mucins. The two i mmunologically diverging mucins nucleated cholesterol from model bile 1-2 days earlier and also caused an almost threefold more rapid ruptur e of cholesterol/phospholipid vesicles than the other mucins. 3. We co nclude that considerable differences exist between mucins derived from individual patients and that the heterogeneity in glycan composition might play a role in the pathogenesis of gallstone disease.