Air pollution particles diminish bacterial clearance in the primed lungs of mice
- Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115 (United States)
- Department of Pharmaceutical Sciences, Massachusetts College of Pharmacy and Health Sciences, Manchester, NH 03101 (United States)
Epidemiological studies reveal increased incidence of lung infection when air pollution particle levels are increased. We postulate that one risk factor for bacterial pneumonia, prior viral infection, can prime the lung for greater deleterious effects of particles via the interferon-gamma (IFN-{gamma}) characteristic of successful host anti-viral responses. To test this postulate, we developed a mouse model in which mice were treated with {gamma}-interferon aerosol, followed by exposure to concentrated ambient particles (CAPs) collected from urban air. The mice were then infected with Streptococcus pneumoniae and the effect of these treatments on the lung's innate immune response was evaluated. The combination of IFN-{gamma} priming and CAPs exposure enhanced lung inflammation, manifest as increased polymorphonuclear granulocyte (PMN) recruitment to the lung, and elevated expression of pro-inflammatory cytokine mRNAs. Combined priming and CAPs exposure resulted in impaired pulmonary bacterial clearance, as well as increased oxidant production and diminished bacterial uptake by alveolar macrophages (AMs) and PMNs. The data suggest that priming and CAPs exposure lead to an inflamed alveolar milieu where oxidant stress causes loss of antibacterial functions in AMs and recruited PMNs. The model reported here will allow further analysis of priming and CAPs exposure on lung sensitivity to infection.
- OSTI ID:
- 21077774
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 223, Issue 1; Other Information: DOI: 10.1016/j.taap.2007.04.014; PII: S0041-008X(07)00209-8; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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