Related Experiment Video
Updated: Aug 11, 2026
Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model
Published on: April 2, 2017
Involvement of the neuropeptide substance P in lung inflammation induced by hepatic ischemia/reperfusion
1Laboratory of Trauma, Sepsis & Inflammation Research, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0558, USA.
Objective And Design:
The purpose of this study was to examine the potential role of substance P in accumulation of neutrophils in the lung following hepatic ischemia/reperfusion.
Materials And Methods:
Male C57BL/6 mice (8-10 weeks of age) were subjected to either sham surgery, partial hepatic ischemia with or without reperfusion, or intratracheal administration of saline or 1 ng substance P. Lung neutrophil accumulation was assessed by tissue content of myeloperoxidase. Activation of the transcription factor, NF-kappaB, was determined by electrophoretic mobility shift assay. Levels of substance P and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage (BAL) fluid was measured using enzyme-linked immunosorbent assays.
Results:
Significant pulmonary neutrophil accumulation was observed just prior to hepatic reperfusion in association with increased BAL levels of substance P. Intratracheal administration of substance P resulted in a similar pattern of neutrophil accumulation which was associated with activation of NF-kappaB and increased BAL levels of the chemokine, MIP-2.
Conclusions:
The data suggest that hepatic ischemia causes substance P release in the lung which activates NF-kappaB leading to the production of MIP-2 and accumulation of neutrophils.
Insights
Hepatic ischemia triggers substance P release in the lungs, activating NF-kappaB and leading to neutrophil accumulation via MIP-2. This study reveals a key pathway in lung injury following liver reperfusion.
Area of Science:
- Immunology
- Physiology
- Gastroenterology
Background:
- Hepatic ischemia/reperfusion (I/R) injury can lead to systemic complications, including acute lung injury.
- Neutrophil infiltration into the lungs is a hallmark of inflammatory responses following I/R.
Purpose of the Study:
- To investigate the role of substance P in mediating neutrophil accumulation in the lungs after hepatic I/R.
- To elucidate the molecular mechanisms linking hepatic I/R to pulmonary inflammation.
Main Methods:
- Murine model of partial hepatic ischemia with or without reperfusion.
- Assessment of lung neutrophil accumulation via myeloperoxidase activity.
- Analysis of nuclear factor-kappaB (NF-kappaB) activation using electrophoretic mobility shift assay.
- Quantification of substance P and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage (BAL) fluid using ELISA.
Main Results:
- Pulmonary neutrophil accumulation correlated with elevated substance P levels in BAL fluid prior to hepatic reperfusion.
- Intratracheal administration of substance P induced neutrophil accumulation, NF-kappaB activation, and increased MIP-2 levels in the lungs.
- These findings suggest a direct role for substance P in initiating the inflammatory cascade.
Conclusions:
- Hepatic ischemia induces substance P release in the lung.
- Substance P activates NF-kappaB, promoting MIP-2 production and subsequent neutrophil recruitment.
- This pathway highlights substance P as a potential therapeutic target for lung injury post-hepatic I/R.
