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Eosinophils alter colonic epithelial barrier function: role for major basic protein.

Glenn T Furuta1, Edward E S Nieuwenhuis, Jorn Karhausen

  • 1Combined Program in Pediatric Gastroenterology and Nutrition, Harvard Medical School, Boston, MA 02115, USA. gfuruta@zeus.bwh.harvard.edu

American Journal of Physiology. Gastrointestinal and Liver Physiology
|October 18, 2005
PubMed
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Eosinophils, particularly major basic protein (MBP), impair intestinal barrier function by downregulating occludin. This finding suggests MBP contributes to inflammatory bowel disease pathogenesis.

Area of Science:

  • Gastroenterology
  • Immunology
  • Cell Biology

Background:

  • Eosinophils are implicated in gastrointestinal diseases with compromised epithelial barrier function.
  • The precise role of eosinophils and their mediators in these conditions remains unclear.

Purpose of the Study:

  • To investigate the impact of eosinophils on intestinal epithelial barrier integrity.
  • To elucidate the specific mechanisms by which eosinophils affect barrier function.

Main Methods:

  • Co-culture of eosinophils with T84 epithelial cells to assess barrier function (transepithelial resistance, TER).
  • Analysis of cell-free supernatants for soluble factors and eosinophil granule proteins (MBP, EDN).
  • Murine model of T helper type 2-mediated colitis (oxazolone-induced) using wild-type and MBP-null mice.

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Main Results:

  • Eosinophil co-culture decreased TER and increased epithelial permeability.
  • A soluble factor, identified as major basic protein (MBP), significantly reduced T84 cell barrier function.
  • MBP was found to downregulate occludin, a key tight junction protein.
  • MBP-null mice exhibited protection against oxazolone-induced colitis.

Conclusions:

  • Eosinophil-derived major basic protein (MBP) directly impairs intestinal epithelial barrier function.
  • Downregulation of occludin is a key mechanism for MBP-induced barrier dysfunction.
  • MBP contributes to the pathogenesis of inflammatory bowel diseases.