Composition of human colonic mucin. Selective alteration in inflammatory bowel disease.

Abstract

A B S T R A C T Human colonic mucin has been isolated from mucosal scrapings of fresh surgical specimens of normal controls as well as patients with Crohn's colitis and ulcerative colitis. Following sonication and ultracentrifugation, mucin fractions were separated from other soluble colonic glycoproteins by Sepharose 4B chromatography. After nuclease digestion, cesium chloride gradient centrifugation of the excluded material yielded colonic mucin with an average buoyant density of 1.52 g/ml. Subsequent chromatography of the apparently homogeneous colonic mucin on DEAEcellulose revealed the presence of at least six distinct mucin species (mucin I-VI). Each mucin species was found to have a distinctive hexose, hexosamine, sialic acid, and sulfate content as well as blood group substance activities. Mucin from five patients with Crohn's colitis was found to represent a mixture of at least six discrete species comparable to those isolated from normal colonic specimens. However, in mucin from eight patients with ulcerative colitis there was a marked and selective reduction of one component mucin subclass, designated species IV. Normal mucin and mucin from patients with Crohn's disease contained 48±17 and 42±12 mg of species IV/g, while mucin from patients with ulcerative colitis had 5±3 mg/g solubilized glycoprotein. The selective absence of species IV was found in preparations from both sigmoid (n = 7) and ascending (n = 4) colon and could not be accounted for by an overall decrease in total mucin content. The selective reduction of species IV was also found in mucin isolated from relatively noninflamed colonic mucosa of patients with ulcerative colitis. The carbohydrate composition and blood group activities of the remaining five mucin species were similar to their normal counterparts. Based on the results to date, there appears to be an underlying selective decrease of one colonic mucin subclass in ulcerative colitis.

Intestinal trefoil factor binds to intestinal epithelial cells and induces nitric oxide production: priming and enhancing effects of mucin

“…Intestinal mucin has been shown to be depleted in patients with IBD [41]. The composition of mucin in patients with Crohn's disease is significantly different from that of normal controls, suggesting that an altered profile of mucin glycoprotein might be present in IBD patients [42,43]. Thus our present findings might provide one explanation for the depletion of intestinal mucin and pathogenesis of IBD.…”

Development of anti-human colonic mucin monoclonal antibodies. Characterization of multiple colonic mucin species.

“…Previous work in this laboratory has suggested the presence of at least six structurally distinct species of mucin glycoprotein in the normal human colon (5,7). The observation of a specific and selective reduction of mucin species IV in association with ulcerative colitis, independent of changes in other mucin components, suggests that distinctions made on the basis of chromatographic and compositional properties reflect biologically meaningful heterogeneity (5,7,32).…”

“…Pure mucin was isolated from materials solubilized by sonication using sequential Sepharose 4B column chromatography and CsCl density centrifugation as previously described (5). Individual mucin species I-VI were separated on DEAE-cellulose column chromatography.…”

“…Purified normal HCM isolated from mucosa of fresh surgical specimens was found to contain at least five distinct mucin species as well as a sixth heterogeneous component recovered in a high salt wash after DEAE-cellulose chromatography (5). Each HCM species (I-VI) appeared to have a distinctive hexose, hexosamine, and amino acid composition, which suggests that the chromatographically defined entities might differ in their fundamental structures.…”

TGF-β Signaling in Dendritic Cells Governs Colonic Homeostasis by Controlling Epithelial Differentiation and the Luminal Microbiota

“…Goblet cell depletion is a histological hallmark of human UC (24,25). Because goblet cell depletion was observed in the histology of CD11c-cre Tgfbr2 fl/fl mice (Fig.…”