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Updated: Aug 11, 2026
Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
CD11b blockade prevents lung injury despite neutrophil priming after gut ischemia/reperfusion
K Koike1, E E Moore, F A Moore
1Department of Surgery, Denver General Hospital and the University of Colorado Health Sciences Center, Denver Colorado.
Abstract:
Gut ischemia/reperfusion (I/R) provokes lung injury via a mechanism that involves neutrophils [polymorphonuclear neutrophils (PMNs)]. CD11b/CD18 (alpha mB2) is the integrin receptor on PMNs critical for adhesion-dependent oxidative burst. The purpose of this study was to investigate the mechanistic role of CD11b in the process of gut I/R-induced lung injury. Sprague-Dawley rats underwent 45 minutes of superior mesenteric artery (SMA) occlusion with and without CD11b monoclonal antibody treatment (IB6) (1 mg/kg, i.v.), before SMA clamping. At 2-hour reperfusion, PMN presence in tissue was quantitated by myeloperoxidase activity and circulating PMN priming determined by the difference in superoxide production with and without N-formyl-methionyl-leucyl-phenylalanine, whereas lung leak was assessed by 125I-albumin lung/blood ratio. In sum, CD11b blockade prevented gut I/R-induced lung leak, but did not attenuate gut I/R-induced PMN priming or tissue PMN accumulation. In conclusion, gut I/R promotes PMN priming and PMN adhesion in both local and distant beds via receptors other than CD11b, but this B2 integrin receptor is critical for PMN-mediated endothelial injury.
Insights
Gut ischemia/reperfusion causes lung injury. Blocking CD11b/CD18 prevents lung leak but not neutrophil priming or accumulation, indicating its critical role in endothelial injury.
Area of Science:
- Gastroenterology
- Pulmonology
- Immunology
Background:
- Gut ischemia/reperfusion (I/R) is a significant cause of distant organ injury, particularly lung injury.
- Neutrophils, specifically polymorphonuclear neutrophils (PMNs), play a crucial role in mediating I/R-induced lung injury.
- The CD11b/CD18 integrin is vital for PMN adhesion and activation, influencing oxidative burst.
Purpose of the Study:
- To elucidate the specific role of the CD11b integrin in the pathogenesis of gut I/R-induced lung injury.
- To investigate whether CD11b blockade can mitigate lung injury following gut I/R.
- To determine the impact of CD11b blockade on PMN priming and tissue infiltration.
Main Methods:
- Sprague-Dawley rats underwent superior mesenteric artery (SMA) occlusion for 45 minutes, with or without CD11b monoclonal antibody (IB6) treatment.
- Myeloperoxidase activity was measured to quantify PMN accumulation in tissues.
- Circulating PMN priming and lung vascular permeability (lung leak) were assessed post-reperfusion.
Main Results:
- CD11b blockade significantly prevented lung leak induced by gut I/R.
- However, CD11b blockade did not attenuate the priming of circulating PMNs.
- Tissue PMN accumulation was also not reduced by CD11b blockade, suggesting alternative adhesion mechanisms.
Conclusions:
- Gut I/R induces PMN priming and adhesion through pathways independent of CD11b.
- The CD11b/CD18 integrin is essential for PMN-mediated endothelial injury, rather than PMN recruitment or activation in this model.
- Targeting CD11b may be a therapeutic strategy to prevent endothelial damage in I/R injury.
