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Updated: Aug 14, 2026
Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
A multi-damage-associated molecular pattern targeting opsonic peptide attenuates gut ischemia/reperfusion-induced
Takayuki Kato1, Takuya Murao1, Atsushi Murao1
1Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY.
Background:
Gut ischemia-reperfusion induces the release of damage-associated molecular patterns (DAMPs), exacerbating inflammation and organ injury and reducing survival. We recently developed a multi-damage-associated molecular pattern scavenging molecule, named opsonic peptide 18, which promotes the clearance of multiple damage-associated molecular patterns by phagocytes. The present study aims to investigate the therapeutic potential of opsonic peptide 18 in gut ischemia-reperfusion-induced lung injury.
Methods:
Male C57BL6/J mice underwent superior mesenteric artery occlusion and were treated with intraperitoneal opsonic peptide 18 or vehicle at the time of reperfusion. Blood and lungs were collected 4 hours after gut ischemia-reperfusion. Systemic levels of interleukin-6, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase were determined. The pulmonary gene expression of cytokines (interleukin-6, interleukin-1β) and chemokines (macrophage-inflammatory protein-2, keratinocyte-derived chemokine) was also assessed. In addition, lung myeloperoxidase activity, tissue injury, and cell death were determined. Mice were monitored for 72 hours after gut ischemia-reperfusion for assessment of overall survival rate.
Results:
Opsonic peptide 18 treatment significantly decreased serum interleukin-6, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels by 45%, 32%, 59%, and 48%, respectively, compared with the vehicle-treated group in gut ischemia-reperfusion mice. Furthermore, opsonic peptide 18 administration decreased mRNA levels of interleukin-6, interleukin-1β, inducible NO synthase, keratinocyte-derived chemokine, and macrophage-inflammatory protein-2 in the lungs by 73.2%, 75.3%, 77.5%, 63.9%, and 64.3%, respectively. Opsonic peptide 18 attenuated myeloperoxidase activity, histologic tissue injury, and cell death in the lungs. Administration of opsonic peptide 18 significantly improved the survival of gut ischemia-reperfusion mice.
Conclusions:
Opsonic peptide 18, a novel multi-damage-associated molecular pattern scavenger, reduces inflammation and mitigates gut ischemia-reperfusion-induced lung injury. Simultaneous targeting of multiple damage-associated molecular patterns is as a promising therapeutic strategy to alleviate gut ischemia-reperfusion-induced lung inflammation and injury.
Insights
Opsonic peptide 18, a novel scavenger of damage-associated molecular patterns (DAMPs), significantly reduced inflammation and lung injury following gut ischemia-reperfusion in mice. This peptide improved survival rates, highlighting its therapeutic potential.
Area of Science:
- Immunology
- Gastroenterology
- Pulmonology
Background:
- Gut ischemia-reperfusion injury releases damage-associated molecular patterns (DAMPs), worsening inflammation and organ damage.
- Opsonic peptide 18 is a novel molecule designed to scavenge multiple DAMPs by promoting phagocytic clearance.
- This study investigates the efficacy of opsonic peptide 18 in mitigating lung injury following gut ischemia-reperfusion.
Purpose of the Study:
- To evaluate the therapeutic potential of opsonic peptide 18 in a mouse model of gut ischemia-reperfusion-induced lung injury.
- To assess the impact of opsonic peptide 18 on systemic inflammation, lung inflammation, and tissue damage.
Main Methods:
- Male C57BL6/J mice underwent superior mesenteric artery occlusion to induce gut ischemia-reperfusion.
- Mice received intraperitoneal opsonic peptide 18 or vehicle at reperfusion.
- Systemic inflammatory markers, pulmonary cytokine and chemokine gene expression, lung myeloperoxidase activity, tissue injury, cell death, and survival rates were assessed.
Main Results:
- Opsonic peptide 18 significantly reduced serum levels of IL-6, AST, ALT, and LDH by 45%, 32%, 59%, and 48%, respectively.
- Pulmonary gene expression of IL-6, IL-1β, iNOS, KC, and MIP-2 was decreased by 73.2%, 75.3%, 77.5%, 63.9%, and 64.3%, respectively.
- Opsonic peptide 18 attenuated lung myeloperoxidase activity, histologic injury, and cell death, significantly improving overall survival.
Conclusions:
- Opsonic peptide 18 effectively reduces inflammation and mitigates lung injury caused by gut ischemia-reperfusion.
- Targeting multiple DAMPs simultaneously presents a promising therapeutic strategy for gut ischemia-reperfusion-induced lung inflammation and injury.
