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Updated: Jul 4, 2026
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
Role of soluble receptor for advanced glycation end products on endotoxin-induced lung injury
Haiying Zhang1, Sadatomo Tasaka, Yoshiki Shiraishi
1Division of Pulmonary Medicine, Keio University School of Medicine, Tokyo, Japan.
Rationale:
The interaction of receptor for advanced glycation end products (RAGE) and its ligands often leads to inflammatory processes or tissue injury, although the effect of the blockade of RAGE signaling on lung injury remains to be investigated.
Objectives:
Using a murine model of lung injury induced by intratracheal lipopolysaccharide (LPS), we evaluated RAGE expression in the airspace and the effect of recombinant soluble RAGE (sRAGE) on LPS-induced lung injury.
Methods:
First, the expression of sRAGE in bronchoalveolar lavage (BAL) fluid was determined at 24 hours after intratracheal instillation of LPS or phosphate-buffered saline. Next, to evaluate the effect of sRAGE, BAL fluid was collected for cell counting and measurements of lung permeability and cytokine concentrations 24 hours after intratracheal LPS in the mice with or without intraperitoneal administration of sRAGE 1 hour after the instillation. In another series, lungs were sampled for histopathology and detection of apoptotic cells. The activation of nuclear factor (NF)-kappaB was analyzed 4 hours after LPS instillation.
Measurements And Main Results:
In response to LPS challenge, a RAGE isoform of 48 kD was detected in the BAL fluid. Treatment with sRAGE significantly attenuated the increases in neutrophil infiltration, lung permeability, production of inflammatory cytokines, NF-kappaB activation, and apoptotic cells in the lung as well as development of pathologic changes after LPS instillation.
Conclusions:
RAGE plays an important role in the pathogenesis of LPS-induced lung injury in mice. It was suggested that sRAGE should be tested as a treatment modality in other models of acute lung injury.
Insights
Receptor for advanced glycation end products (RAGE) blockade with soluble RAGE (sRAGE) significantly reduced inflammation and injury in a mouse model of acute lung injury. This suggests sRAGE may be a potential therapeutic for lung damage.
Area of Science:
- Pulmonary Medicine
- Immunology
- Molecular Biology
Background:
- Receptor for advanced glycation end products (RAGE) and its ligands are implicated in inflammatory processes and tissue injury.
- The role of RAGE signaling blockade in acute lung injury remains unclear.
Purpose of the Study:
- To investigate RAGE expression in lipopolysaccharide (LPS)-induced lung injury.
- To evaluate the therapeutic effect of recombinant soluble RAGE (sRAGE) on LPS-induced lung injury in a murine model.
Main Methods:
- Mice received intratracheal LPS to induce lung injury.
- RAGE expression in bronchoalveolar lavage (BAL) fluid was measured.
- Mice were treated with sRAGE to assess its impact on lung permeability, inflammatory cytokines, neutrophil infiltration, NF-kappaB activation, and apoptosis.
- Histopathology and apoptotic cell detection were performed.
Main Results:
- LPS challenge increased RAGE expression in BAL fluid.
- sRAGE treatment significantly reduced neutrophil infiltration, lung permeability, and inflammatory cytokine levels.
- sRAGE also attenuated NF-kappaB activation, apoptotic cells, and pathological changes in the lungs.
Conclusions:
- RAGE is a key mediator in the pathogenesis of LPS-induced acute lung injury in mice.
- sRAGE demonstrates therapeutic potential and warrants further investigation in other acute lung injury models.
