Related Experiment Video
Updated: Jul 9, 2025
Visualizing Lung Cellular Adaptations during Combined Ozone and LPS Induced Murine Acute Lung Injury
Published on: March 21, 2021
Ambient atmospheric PM worsens mouse lung injury induced by influenza A virus through lysosomal dysfunction
Shunwang Li1, Xiangwu Ju1, Qiang Liu1
1State Key Laboratory of Common Mechanism Research for Major Diseases, School of Basic Medicine Peking Union Medical College, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Beijing, 100005, China.
Background:
Particulate matter (PM) air pollution poses a significant risk to respiratory health and is especially linked with various infectious respiratory diseases such as influenza. Our previous studies have shown that H5N1 virus infection could induce alveolar epithelial A549 cell death by enhancing lysosomal dysfunction. This study aims to investigate the mechanisms underlying the effects of PM on influenza virus infections, with a particular focus on lysosomal dysfunction.
Results:
Here, we showed that PM nanoparticles such as silica and alumina could induce A549 cell death and lysosomal dysfunction, and degradation of lysosomal-associated membrane proteins (LAMPs), which are the most abundant lysosomal membrane proteins. The knockdown of LAMPs with siRNA facilitated cellular entry of both H1N1 and H5N1 influenza viruses. Furthermore, we demonstrated that silica and alumina synergistically increased alveolar epithelial cell death induced by H1N1 and H5N1 influenza viruses by enhancing lysosomal dysfunction via LAMP degradation and promoting viral entry. In vivo, lung injury in the H5N1 virus infection-induced model was exacerbated by pre-exposure to silica, resulting in an increase in the wet/dry ratio and histopathological score.
Conclusions:
Our findings reveal the mechanism underlying the synergistic effect of nanoparticles in the early stage of the influenza virus life cycle and may explain the increased number of respiratory patients during periods of air pollution.
Insights
Particulate matter nanoparticles like silica and alumina worsen influenza virus infections by damaging lung cells and increasing viral entry. This explains why respiratory illnesses rise during air pollution.
Area of Science:
- Environmental Health
- Virology
- Toxicology
Background:
- Particulate matter (PM) air pollution is linked to increased respiratory infections, including influenza.
- Previous research indicated H5N1 influenza virus infection causes alveolar epithelial cell death via lysosomal dysfunction.
Purpose of the Study:
- To investigate the mechanisms by which PM affects influenza virus infections.
- To specifically examine the role of lysosomal dysfunction in PM-mediated exacerbation of influenza.
Main Methods:
- Exposure of A549 alveolar epithelial cells to PM nanoparticles (silica, alumina).
- Assessment of cell death, lysosomal dysfunction, and lysosomal-associated membrane proteins (LAMPs) degradation.
- RNA interference (siRNA) to knock down LAMPs and evaluate its effect on viral entry.
- In vivo studies using an H5N1 virus infection model with silica pre-exposure.
Main Results:
- PM nanoparticles (silica, alumina) induced A549 cell death and lysosomal dysfunction, including LAMP degradation.
- LAMP knockdown enhanced H1N1 and H5N1 influenza virus entry into cells.
- Silica and alumina synergistically increased influenza virus-induced cell death by promoting lysosomal dysfunction and viral entry.
- In vivo, silica pre-exposure exacerbated H5N1-induced lung injury.
Conclusions:
- Nanoparticles like silica and alumina impair lysosomal function, facilitating influenza virus entry and replication.
- This mechanism explains the synergistic effect of PM on influenza virus infection.
- Findings may elucidate the rise in respiratory illnesses during periods of high air pollution.
