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

Abstract

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