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Published on: December 18, 2010
The macrophages regulate intestinal motility dysfunction through the PGE2 Ptger3 axis during Klebsiella pneumonia
1Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.
Introduction:
Gut motility dysfunction, the most common complication of post-septic organ dysfunction, depends on immune and neuronal cells. This study aimed to investigate the mechanisms that activate these cells and the contribution of macrophages to the recovery of intestinal motility dysfunction after sepsis.
Materials And Methods:
Postoperative gut motility dysfunction was induced by establishing Klebsiella pneumonia sepsis in mice with selective deletion of neutrophils and macrophages in the gut. The distribution of orally administered fluorescein isothiocyanate-dextran and carmine excretion time was used to determine the severity of small bowel disease. The effect of macrophages on intestinal motility was evaluated after prostaglandin E2 therapy.
Results:
We found that muscular neutrophil infiltration leading to neuronal loss in the intestine muscle triggered intestinal motility dysfunction after pneumonia sepsis; however, reduced neutrophil infiltration did not improve intestinal motility dysfunction. Moreover, macrophage depletion aggravated gut motility dysfunction. The addition of macrophages directly to a smooth muscle was responsible for the recovery of intestinal motility.
Conclusion:
Our results suggest that a direct interaction between macrophages and smooth muscle is neurologically independent of the restoration of intestinal dysmotility.
Insights
Macrophages are crucial for restoring gut motility after sepsis. Direct interaction between macrophages and smooth muscle aids recovery, independent of neural pathways, highlighting a key mechanism in gut health post-infection.
Area of Science:
- Gastroenterology
- Immunology
- Neuroscience
Background:
- Gut motility dysfunction is a common complication following sepsis.
- Immune and neuronal cells are critical for gut function.
- Understanding the role of immune cells in gut recovery is essential.
Purpose of the Study:
- To investigate mechanisms activating immune and neuronal cells in sepsis-induced gut dysfunction.
- To determine the contribution of macrophages to intestinal motility recovery after sepsis.
Main Methods:
- Sepsis-induced gut motility dysfunction in mice with selective neutrophil and macrophage deletion.
- Assessing small bowel disease severity using fluorescein isothiocyanate-dextran and carmine excretion.
- Evaluating macrophage effects on intestinal motility with prostaglandin E2 therapy.
Main Results:
- Neutrophil infiltration and subsequent neuronal loss in intestinal muscle caused motility dysfunction.
- Macrophage depletion worsened gut motility dysfunction.
- Direct addition of macrophages to smooth muscle restored intestinal motility.
Conclusions:
- Macrophages play a vital role in restoring intestinal motility post-sepsis.
- Macrophage-smooth muscle interaction is key for recovery, independent of neural mechanisms.
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