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Updated: Aug 29, 2026
Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
Microcirculatory dysfunction during intestinal ischemia-reperfusion
1Institute of Surgical Research, University of Szeged, Szeged, Hungary. boros@expsur.szote.u-szeged.hu
Abstract:
Oxido-reductive stress is a crucial factor of the tissue response during ischemia-reoxygenation injuries. Reperfusion affects primarily the microvasculature in a manner consistent with an acute inflammatory reaction. In this respect, the salient data suggest an important connection between endothelial cell-derived humoral mediators and the perivascular mast cell system. Increased endothelin-1 and decreased nitric oxide formation, mast cell degranulation and leukocyte accumulation coexist in gastrointestinal ischemia-reperfusion syndromes too. Constitutively produced nitric oxide inhibits, while increasingly formed endothelin-1 significantly enhances the degranulation of the intestinal mast cells. The endothelin-A receptor-dependent mast cell degranulation per se plays a secondary role in reperfusion-induced structural injury, but contributes significantly to leukocyte recruitment into the reperfused intestinal mucosa. It is conceivable therefore, that the nitric oxide--endothelin-1--mast cell cycle is involved in the mechanism of ischemia-reperfusion-induced endothelial cell-leukocyte interactions, where mast cells act to amplify the process of leukocyte sequestration. The alteration in the balance between endothelial cell-derived proadhesive vasoconstrictor and antiadhesive vasodilator factors exerts a significant influence on the mucosal integrity, and the antagonism of endothelin-A receptor activation in this setting tips the equilibrium toward tissue salvage.
Insights
Oxidative stress during ischemia-reperfusion injury involves a cycle where endothelin-1 enhances mast cell degranulation, promoting leukocyte recruitment. Blocking endothelin-A receptors aids tissue recovery by restoring balance.
Area of Science:
- Physiology
- Pathology
- Immunology
Background:
- Ischemia-reperfusion (I/R) injury involves oxidative stress and microvascular inflammation.
- Endothelial cells and mast cells interact during I/R, influencing leukocyte recruitment.
- Gastrointestinal I/R syndromes show links between endothelin-1, nitric oxide, and mast cell activity.
Purpose of the Study:
- To investigate the role of the nitric oxide-endothelin-1-mast cell axis in I/R-induced endothelial cell-leukocyte interactions.
- To determine the contribution of mast cell degranulation to reperfusion injury and leukocyte accumulation.
- To evaluate the therapeutic potential of endothelin-A receptor antagonism in I/R injury.
Main Methods:
- Analysis of humoral mediators (endothelin-1, nitric oxide) in I/R models.
- Assessment of mast cell degranulation and leukocyte infiltration in the intestinal mucosa.
- Investigation of endothelin-A receptor involvement in mast cell activation and tissue injury.
Main Results:
- Nitric oxide inhibits, while endothelin-1 enhances intestinal mast cell degranulation.
- Endothelin-A receptor-mediated mast cell degranulation contributes significantly to leukocyte recruitment, not structural injury.
- The nitric oxide-endothelin-1-mast cell pathway amplifies leukocyte sequestration during intestinal I/R.
Conclusions:
- Mast cells act as amplifiers in the I/R-induced endothelial cell-leukocyte interaction cascade.
- Modulating the balance between vasoconstrictors and vasodilators is key to preserving mucosal integrity.
- Antagonizing endothelin-A receptor activation promotes tissue salvage in I/R injury.
