A novel human macrophage-derived intestinal mucin secretagogue: Implications for the pathogenesis of inflammatory bowel disease

Kirk Sperber, Shunichiro Ogata, Clewert Sylvester, James Aisenberg, Anli Chen, Lloyd Mayer, Steven Itzkowitz

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Background: A novel 68-kilodalton macrophage-derived protein (MMS-68) stimulating mucin release from respiratory epithelial cells has previously been described. In this study, the effect of MMS-68 on mucin release from intestinal epithelial cells was determined. Methods: Colonic epithelial cells isolated from normal colon, ulcerative colitis, Crohn's colitis, and cells from three colon cancer cell lines were labeled with [3H]-glucosamine and stimulated with MMS-68. High molecular weight glycoproteins were precipitated and counted. Results: In all of the cells tested, MMS-68 enhanced mucin secretion by 1.46-2.0-fold above control values, comparable to the level achieved with carbachol (10-5 mol/L). Coincubation with anti-MMS-68 monoclonal antibody 1D-10 blocked this bioactivity. Freshly isolated intestinal macrophages reacted with monoclonal antibody 1D-10. Immunofluorescent staining of frozen sections revealed the presence of MMS-68-producing cells (macrophages) in the lamina propria of normal colon and Crohn's colitis, with weaker expression in ulcerative colitis mucosa. Conclusions: Intestinal macrophages produce a novel mucin secretagogue, which is as potent as carbachol for stimulating mucin secretion from colonic epithelial cells. This factor may explain, in part, the alterations in mucin secretion often seen in inflammatory bowel disease.

Original languageEnglish
Pages (from-to)1302-1309
Number of pages8
JournalGastroenterology
Volume104
Issue number5
DOIs
StatePublished - May 1993

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