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Effects of exposure to peroxyacetyl nitrate on susceptibility to acute and chronic bacterial infection
Abstract:
A significant increase in mortality due to acute respiratory pneumonia caused by inhalation of Streptococcus pyogenes aerosol was seen after a single 3-h exposure of mice to 14.8-28.4 mg/m3 peroxyacetyl nitrate (PAN). The excess mortality ranged from 8 to 39% and the decrease in survival time from 2.4 to 7.9 d. A single exposure to 25.0 mg/m3 PAN resulted in a significant increase in total number of cells lavaged from the lungs but somewhat decreased levels of adenosine triphosphate (ATP) in alveolar macrophages. Exposure to 7.4 mg/m3 PAN for 3 h/d, 5 d/wk, for 2 wk resulted in a reduced total count of free pulmonary cells and a significant reduction of ATP levels in alveolar macrophages but had no effect on mortality or survival rate. Scanning electron microscopic observations of the respiratory tract after both single and multiple exposures to PAN showed raised and sloughing nonciliated cells in the nasal cavities and tracheas and presence of excess mucus. Six daily 3-h exposures to 25.0 mg/m3 PAN did not produce any marked changes in a chronic respiratory infection in mice as measured by Mycobacterium tuberculosis lung titers.
Insights
Exposure to peroxyacetyl nitrate (PAN) significantly increased mortality in mice infected with Streptococcus pyogenes. Even short exposures damaged respiratory tissues and altered immune cell function, highlighting PAN
Area of Science:
- Environmental Toxicology
- Pulmonary Toxicology
- Infectious Disease Immunology
Background:
- Peroxyacetyl nitrate (PAN) is a common air pollutant.
- PAN's effects on respiratory infections and immune responses are not fully understood.
Purpose of the Study:
- To investigate the impact of PAN exposure on acute respiratory pneumonia caused by Streptococcus pyogenes.
- To assess the effects of single and repeated PAN exposures on pulmonary immune cell counts, function, and respiratory tract histology.
Main Methods:
- Mice were exposed to varying concentrations of PAN via aerosol.
- Mortality, survival time, lung lavage cell counts, adenosine triphosphate (ATP) levels in alveolar macrophages, and respiratory tract histology were assessed.
- Chronic respiratory infection models were used to evaluate PAN's effect on Mycobacterium tuberculosis lung titers.
Main Results:
- A single 3-h exposure to PAN (14.8-28.4 mg/m3) significantly increased mortality and decreased survival time in mice with Streptococcus pyogenes pneumonia.
- Single high-dose PAN exposure increased lung lavage cells and decreased ATP levels in alveolar macrophages.
- Repeated low-dose PAN exposure reduced pulmonary cells and ATP levels but did not affect mortality.
- Histological examination revealed respiratory tract damage, including cell sloughing and mucus production.
Conclusions:
- Acute PAN exposure exacerbates Streptococcus pyogenes-induced pneumonia, increasing mortality and reducing survival.
- PAN exposure induces pulmonary inflammation and impairs alveolar macrophage function.
- Repeated low-level PAN exposure may lead to subclinical respiratory tract damage and immune dysfunction without increasing mortality.