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Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
Establishment of particulate matter-induced lung injury model in mouse
Se Yong Park1, Kyu Sup An2, Buhyun Lee3
1Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul, 08826, South Korea.
Background:
Particulate matter (PM) is one of the principal causes of human respiratory disabilities resulting from air pollution. Animal models have been applied to discover preventive and therapeutic drugs for lung diseases caused by PM. However, the induced severity of lung injury in animal models using PM varies from study to study due to disparities in the preparation of PM, and the route and number of PM administrations. In this study, we established an in vivo model to evaluate PM-induced lung injury in mice.
Results:
PM dispersion was prepared using SRM2975. Reactive oxygen species were increased in MLE 12 cells exposed to this PM dispersion. In vivo studies were conducted in the PM single challenge model, PM multiple challenge model, and PM challenge with ovalbumin-induced asthma using the PM dispersion. No histopathological changes were observed in lung tissues after a single injection of PM, whereas mild to moderate lung inflammation was obtained in the lungs of mice exposed to PM three times. However, fibrotic changes were barely seen, even though transmission electron microscopy (TEM) studies revealed the presence of PM particles in the alveolar macrophages and alveolar capillaries. In the OVA-PM model, peribronchial inflammation and mucous hypersecretion were more severe in the OVA+PM group than the OVA group. Serum IgE levels tended to increase in OVA+PM group than in OVA group.
Conclusions:
In this study, we established a PM-induced lung injury model to examine the lung damage induced by PM. Based on our results, repeated exposures of PM are necessary to induce lung inflammation by PM alone. PM challenge, in the presence of underlying diseases such as asthma, can also be an appropriate model for studying the health effect of PM.
Insights
Repeated exposure to particulate matter (PM) is necessary to cause lung inflammation in mice. PM exposure exacerbates asthma symptoms, making it a useful model for studying air pollution
Area of Science:
- Environmental Health
- Toxicology
- Pulmonology
Background:
- Particulate matter (PM) is a major air pollutant causing respiratory diseases.
- Existing animal models for PM-induced lung injury lack standardization.
- Variability in PM preparation and administration affects injury severity.
Purpose of the Study:
- To establish and validate an in vivo mouse model for evaluating PM-induced lung injury.
- To investigate the effects of single versus multiple PM exposures.
- To assess PM's impact on an asthma model.
Main Methods:
- Standardized PM dispersion (SRM2975) was prepared.
- Mice were subjected to single or multiple PM challenges.
- An ovalbumin-induced asthma model was combined with PM challenge.
- Lung histology, TEM, and serum IgE levels were analyzed.
Main Results:
- Single PM exposure caused no histopathological changes.
- Multiple PM exposures led to mild to moderate lung inflammation.
- PM particles were found in alveolar macrophages and capillaries.
- PM challenge worsened airway inflammation and mucous hypersecretion in the asthma model.
- Serum IgE levels showed a trend of increase in the asthma+PM group.
Conclusions:
- Repeated PM exposure is required to induce lung inflammation solely by PM.
- The established model is suitable for studying PM health effects, especially in the context of pre-existing conditions like asthma.
