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Development of an Antigen-driven Colitis Model to Study Presentation of Antigens by Antigen Presenting Cells to T Cells
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A novel human macrophage-derived intestinal mucin secretagogue: implications for the pathogenesis of inflammatory

K Sperber1, S Ogata, C Sylvester

  • 1Division of Clinical Immunology, Mount Sinai Medical Center, New York, New York.

Gastroenterology
|May 1, 1993
PubMed
Abstract

Insights

Intestinal macrophages release a novel protein, MMS-68, that significantly enhances mucin secretion from colon cells. This finding may help explain changes in mucin observed in inflammatory bowel diseases.

Area of Science:

  • Gastroenterology
  • Immunology
  • Cell Biology

Background:

  • A novel 68-kilodalton macrophage-derived protein (MMS-68) was previously identified as a stimulator of mucin release from respiratory epithelial cells.
  • The current study investigates the role of MMS-68 in modulating mucin release from intestinal epithelial cells.

Purpose of the Study:

  • To determine the effect of MMS-68 on mucin secretion from various colonic cell types.
  • To investigate the source and distribution of MMS-68 in the colon.

Main Methods:

  • Colonic epithelial cells from normal and diseased tissues, including ulcerative colitis and Crohn's colitis, along with colon cancer cell lines, were utilized.
  • Cells were labeled with [3H]-glucosamine, stimulated with MMS-68, and high molecular weight glycoproteins were precipitated and quantified.
  • Immunofluorescent staining and monoclonal antibody assays were employed to identify MMS-68-producing cells and block its bioactivity.

Main Results:

  • MMS-68 significantly enhanced mucin secretion across all tested colonic cell types by 1.46-2.0-fold.
  • The observed enhancement was comparable to that induced by carbachol.
  • Neutralization with anti-MMS-68 monoclonal antibody 1D-10 abolished the stimulatory effect, and MMS-68-producing macrophages were identified in the colonic lamina propria.

Conclusions:

  • Intestinal macrophages produce a novel mucin secretagogue (MMS-68) that potently stimulates colonic epithelial cell mucin secretion.
  • This macrophage-derived factor may contribute to the altered mucin secretion patterns observed in inflammatory bowel diseases.

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