title: Air pollution particles diminish bacterial clearance in the primed lungs of mice.
abstract: 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.
authors.affiliation: Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Sigaud
authors.forename: Carroll-Ann W
authors.initials: CA
authors.lastname: Goldsmith
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhou
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Yang
authors.forename: Alexey
authors.initials: A
authors.lastname: Fedulov
authors.forename: Amy
authors.initials: A
authors.lastname: Imrich
authors.forename: Lester
authors.initials: L
authors.lastname: Kobzik
mesh_terms: D000336:Aerosols; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D002947:Cities; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D019570:Inhalation Exposure / Q000009:adverse effects; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018375:Neutrophil Activation / Q000187:drug effects / Q000276:immunology; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000276:immunology*
chemical_list: D000336:Aerosols; D000393:Air Pollutants; D016207:Cytokines; D052638:Particulate Matter; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D007371:Interferon-gamma