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Generation of a Chronic Obstructive Pulmonary Disease Model in Mice by Repeated Ozone Exposure

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The Acrolein-Lipopolysaccharide Mouse Model for Frequent Exacerbations in Chronic Obstructive Pulmonary Disease.

Bernhard Fe Reiter^1,2, Natalie Bordag^1,3, Diana Schnoegl¹

¹Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.

American Journal of Respiratory Cell and Molecular Biology

|May 9, 2025

Summary

A new mouse model for chronic obstructive pulmonary disease (COPD) uses lipopolysaccharide (LPS) and acrolein (Acro) for faster, more representative disease study. This model reveals key inflammatory and metabolic changes, aiding COPD research.

Keywords:

COPD acrolein inflammation lipopolysaccharide mouse model

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Area of Science:

Pulmonary Medicine
Immunology
Metabolomics

Background:

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease with limited pre-clinical models.
Existing models like smoke or elastase have drawbacks, including long durations and insufficient pathophysiological detail.

Purpose of the Study:

To develop a novel, time-efficient mouse model for studying COPD.
To investigate the immunological and metabolomic changes induced by this new model.

Main Methods:

Mice were treated weekly for four weeks with bacterial lipopolysaccharide (LPS) and acrolein (Acro).
Histological analysis, multicolour flow cytometry, and nuclear magnetic resonance (NMR) were used to assess changes.
Dexamethasone was used to evaluate therapeutic intervention.

Main Results:

Acro/LPS treatment induced moderate airspace enlargement and bronchial remodelling.
Significant increases in macrophages, T-helper cells, and specific cytokines (CXCL11, IL-17a, TNF-α) were observed.
Metabolomic analysis revealed elevated COPD-associated metabolites and altered energy metabolism.

Conclusions:

The Acro/LPS mouse model is a practical, representative, and time-efficient tool for COPD research.
This model allows for the study of COPD's immunological and pathophysiological development.
Dexamethasone intervention demonstrated potential therapeutic effects on inflammation and histology.