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Role of neutrophils in ischemia-reperfusion-induced microvascular injury
Abstract:
Recent studies indicate that polymorphonuclear neutrophils (PMNs) infiltrate the intestinal mucosa during ischemia and after reperfusion. To determine whether PMNs mediate the increased microvascular permeability produced by ischemia-reperfusion (I/R) we treated cats with either saline, antineutrophil serum (ANS), or a monoclonal antibody specific for the beta-chain of the CD18 complex (MoAb 60.3) that prevents neutrophil adherence and extravasation. Intestinal microvascular permeability to plasma proteins was measured in control preparations (0.08 +/- 0.007), in preparations subjected to 1 h of ischemia then reperfusion (I/R, 0.32 +/- 0.02), I/R preparations treated with ANS (0.13 +/- 0.01), and I/R preparations treated with MoAb (0.12 +/- 0.003). Our results indicate that both PMN depletion (to less than 10% control) and prevention of PMN adherence significantly attenuate the increased microvascular permeability induced by I/R. These findings, coupled to previous results obtained from this model, support the hypothesis that neutrophils, which accumulate in the mucosa in response to xanthine oxidase activation, mediate the oxyradical-dependent injury produced by reperfusion of the ischemic bowel.
Insights
Polymorphonuclear neutrophils (PMNs) increase intestinal permeability after ischemia-reperfusion injury. Depleting PMNs or blocking their adherence significantly reduces this permeability, indicating neutrophils mediate this damage.
Area of Science:
- Gastroenterology
- Immunology
- Vascular Biology
Background:
- Polymorphonuclear neutrophils (PMNs) are known to infiltrate the intestinal mucosa following ischemia and reperfusion (I/R).
- Previous research suggests a potential role for PMNs in I/R-induced microvascular injury.
Purpose of the Study:
- To investigate whether PMNs are the primary mediators of increased microvascular permeability caused by intestinal ischemia-reperfusion.
- To determine the specific mechanisms by which PMNs contribute to I/R injury.
Main Methods:
- Experiments were conducted on cats subjected to 1 hour of intestinal ischemia followed by reperfusion.
- Animals were treated with saline, antineutrophil serum (ANS) to deplete PMNs, or a monoclonal antibody (MoAb 60.3) to inhibit neutrophil adherence.
- Intestinal microvascular permeability to plasma proteins was measured in all groups.
Main Results:
- Ischemia-reperfusion significantly increased intestinal microvascular permeability compared to controls.
- Treatment with ANS or MoAb 60.3 markedly reduced the permeability increase observed in I/R preparations.
- PMN depletion to less than 10% of control levels and prevention of PMN adherence both significantly attenuated I/R-induced permeability.
Conclusions:
- Neutrophils play a critical role in mediating the increased microvascular permeability associated with intestinal ischemia-reperfusion injury.
- These findings support the hypothesis that neutrophils, activated by xanthine oxidase, contribute to the oxyradical-dependent damage during reperfusion of the ischemic bowel.