Sulphation of colonic and rectal mucin in inflammatory bowel disease: reduced sulphation of rectal mucus in ulcerative colitis

Abstract

1. Normal colonic mucin is heavily sulphated and this increases its resistance to degradation by bacterial enzymes. Any defect in mucus sulphation could therefore be important in the pathogenesis of ulcerative colitis. 2. Rectal biopsies taken at colonoscopy from patients with ulcerative colitis (n = 9), patients with Crohn's disease (n = 6) and control subjects (n = 16) were cultured for 24 h in the presence of N-[3H]acetyl-glucosamine and [35S]sulphate. Mucin was then extracted and purified, and the ratio of [35S]sulphate to N-[3H]acetyIglucosamine incorporated into pure mucin was assessed. 3. The ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into mucin was significantly reduced in rectal biopsies taken from patients with ulcerative colitis (0.463, 0.305–0.703, geometric mean and 95% confidence intervals) compared with control subjects (0.857, 0.959–1.111, P<0.01). In patients with Crohn's disease the reduction in this ratio (0.559, 0.378–0.829) did not quite reach statistical significance (P=0.06). There was no difference between the ratio of [35S]sulphate to N-[3H]acetyl-glucosamine incorporated into mucin in Crohn's disease and that in ulcerative colitis (P = 0.26). 4. In control subjects the ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into mucin was higher in the rectal biopsies (0.882, 0.618–1.022) than in their paired proximal colonic biopsies (0.602, 0.421–0.861; P<0.01), but this regional variation was not observed in either ulcerative colitis (rectum: 0.450, 0.262–0.773; right colon: 0.470, 0.321–0.690, P = 0.3) or Crohn's disease (rectum: 0.459, 0.260–0.815; right colon: 0.492, 0.260–0.929, P = 0.8). 5. There was no significant difference in N-[3H]acetylglucosamine incorporation among the three groups (control subjects: 21195, 16611–32695 d.p.m./mg of biopsy protein content; ulcerative colitis: 12108, 7663-21 548 d.p.m./mg of biopsy protein content; Crohn's disease: 14 891, 8620-34 419 d.p.m./mg of biopsy protein content, P = 0.17), suggesting that there is a selective reduction of incorporation of sulphate per mucin side chain. 6. This study demonstrates a reduced ability of the rectal mucosa to sulphate mucin in patients with inflammatory bowel disease.