Related Experiment Video
Updated: May 10, 2026
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
A single dose of lipopolysaccharide into mice with emphysema mimics human chronic obstructive pulmonary disease
Satoshi Kobayashi1, Reiko Fujinawa, Fumi Ota
11 Disease Glycomics Team and.
Abstract:
Chronic obstructive pulmonary disease (COPD), manifested as emphysema and chronic airway obstruction, can be exacerbated by bacterial and viral infections. Although the frequency of exacerbations increases as the disease progresses, the mechanisms underlying this phenomenon are largely unknown, and there is a need for a simple in vivo exacerbation model. In this study, we compared four groups of mice treated with PBS alone, elastase alone, LPS alone, and elastase plus LPS. A single intratracheal administration of LPS to mice with elastase-induced emphysema provoked infiltration of inflammatory cells, especially CD8(+) T cells, into alveolar spaces and increased matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and perforin production in bronchoalveolar lavage fluid at the acute inflammatory phase compared with the other groups. We also measured the percentage of low-attenuation area (LAA%) in the above mice using micro-computed X-ray tomography. The LAA% was the most sensitive parameter for quantitative assessments of emphysema among all the parameters evaluated. Using the parameter of LAA%, we found significantly more severe alveolar destruction in the group treated with elastase plus LPS compared with the other groups during long-term longitudinal observations. We built three-dimensional images of the emphysema and confirmed that the lungs of elastase plus LPS-treated mice contained larger emphysematous areas than mice treated with elastase alone. Although human exacerbation of COPD is clinically and pathologically complicated, this simple mouse model mimics human cases to some extent and will be useful for elucidating its mechanism and developing therapeutic strategies.
Insights
Researchers developed a simple mouse model for chronic obstructive pulmonary disease (COPD) exacerbations. This model, using elastase and LPS, effectively mimics human COPD exacerbations, aiding in mechanism elucidation and therapeutic development.
Area of Science:
- Pulmonary Medicine
- Animal Models
- Inflammation Research
Background:
- Chronic obstructive pulmonary disease (COPD) exacerbations are frequent and increase with disease severity.
- Mechanisms underlying COPD exacerbations remain poorly understood.
- A simple in vivo model is needed to study COPD exacerbations.
Purpose of the Study:
- To develop and validate a simple in vivo mouse model for COPD exacerbations.
- To investigate the inflammatory and structural changes associated with COPD exacerbation in this model.
Main Methods:
- Induction of emphysema in mice using elastase.
- Administration of lipopolysaccharide (LPS) to induce exacerbation.
- Assessment of inflammatory cell infiltration (CD8+ T cells) and protein production (MMP-9, TIMP-1, perforin) in bronchoalveolar lavage fluid.
- Quantitative assessment of emphysema severity using micro-computed tomography (micro-CT) to measure low-attenuation area (LAA%).
- Longitudinal observation and 3D imaging of lung structure.
Main Results:
- Intratracheal LPS administration in elastase-induced emphysema models significantly increased inflammatory cell infiltration and specific protein levels.
- Low-attenuation area percentage (LAA%) measured by micro-CT was a sensitive indicator of emphysema severity.
- The elastase plus LPS group exhibited significantly more severe alveolar destruction and larger emphysematous areas compared to controls.
- The developed mouse model demonstrated key pathological features of human COPD exacerbations.
Conclusions:
- A simple mouse model combining elastase and LPS effectively mimics key aspects of human COPD exacerbations.
- This model provides a valuable tool for investigating the mechanisms of COPD exacerbations.
- The model can facilitate the development and testing of novel therapeutic strategies for COPD exacerbations.
