Mast cells trigger epithelial barrier dysfunction, bacterial translocation and postoperative ileus in a mouse model

Area of Science:

• Gastroenterology
• Immunology
• Surgical Research

Background:

• Abdominal surgery and bowel manipulation can lead to inflammation, impaired motility, and postoperative ileus (POI).
• Mast cells are implicated in POI pathogenesis in preclinical and clinical studies.
• The role of mast cells in eliciting intestinal barrier dysfunction requires further investigation.

Purpose of the Study:

• To investigate the contribution of mast cells to intestinal barrier dysfunction following abdominal surgery.
• To determine if mast cell activation during surgery exacerbates bowel inflammation and barrier defects.

Main Methods:

• Comparison of wild-type (WT) mice with mast cell-deficient (Kit(W/W-v) and Kit(W-sh/W-sh)) mice undergoing laparotomy or intestinal manipulation (IM).
• Assessment of postoperative inflammatory infiltrates, cytokine production, and neutrophil extravasation.
• Evaluation of epithelial barrier function using Ussing chambers, particle transport assays, and bacterial translocation measurements.

Main Results:

• Intestinal manipulation induced pro-inflammatory responses and neutrophil infiltration in WT mice, which were reduced in mast cell-deficient mice.
• Epithelial barrier dysfunction was observed in WT mice post-IM but not in mast cell-deficient strains.
• Impaired barrier function was attributed to mast cell mediators, not tissue hypoperfusion, as mean arterial pressure decreased similarly in all groups.

Conclusions:

• Mast cell activation during abdominal surgery contributes to epithelial barrier dysfunction and inflammation of the bowel's muscularis externa.
• Compromised epithelial barrier function is a likely factor in the pathogenesis of postoperative ileus.
• Mast cells represent a potential cellular target for therapeutic strategies aimed at ameliorating POI.