Sulphation and secretion of the predominant secretory human colonic mucin MUC2 in ulcerative colitis

Background-Decreased synthesis of the predominant secretory human colonic mucin (MUC2) occurs during active ulcerative colitis. Aims-To study possible alterations in mucin sulphation and mucin secretion, which could be the cause of decreased mucosal protection in ulcerative colitis. Methods-Colonic biopsy specimens from patients with active ulcerative colitis, ulcerative colitis in remission, and controls were metabolically labelled with [S-35]-amino acids or [S-35]-sulphate, chase incubated and analysed by SDS-PAGE, followed by quantitation of mature [S-35]- labelled MUC2. For quantitation of total MUC2, which includes non-radiolabelled and radiolabelled MUC2, dot blotting was performed, using a MUC2 monoclonal antibody. Results-Between patient groups, no significant differences were found in [S-35]-sulphate content of secreted MUC2 or in the secreted percentage of either [S-35]-amino acid labelled MUC2 or total MUC2. During active ulcerative colitis, secretion of [S-35]-sulphate labelled MUC2 was significantly increased twofold, whereas [S-35]-sulphate incorporation into MUC2 was significantly reduced to half. Conclusions-During active ulcerative colitis, less MUC2 is secreted, because MUC2 synthesis is decreased while the secreted percentage of MUC2 is unaltered. Furthermore, sulphate content of secreted MUC2 is unaltered by a specific compensatory mechanism, because sulphated MUC2 is preferentially secreted while sulphate incorporation into MUC2 is reduced.