Long-term exposure to diesel exhaust enhances antigen-induced eosinophilic inflammation and epithelial damage in the murine airway.
The histopathologic changes in the murine airway induced by long-term exposure to diesel exhaust (DE), ovalbumin (OA), or both were investigated. The relationship between the histopathologic appearances in the airway and immunoglobulin production or local cytokine levels in the lungs was also studied. ICR mice were exposed to clean air or DE at a soot concentrations of 0.3, 1.0, or 3.0 mg/m3 for 34 weeks. Fifteen weeks after exposure to DE, mice were sensitized intraperitoneally with 10 micrograms of OA and challenged by an aerosol of 1% OA six times at 3-week intervals during the last 18 weeks of the exposure. DE exposure caused a dose-dependent increase of nonciliated cell proliferation and epithelial cell hypertrophy in the airway, but showed no effect on goblet cell proliferation in the bronchial epithelium and eosinophil recruitment in the submucosa of the airway. OA treatment induced very slight changes in goblet cell proliferation and eosinophil recruitment. The combination of OA and DE exposure produced dose-dependent increases of goblet cells and eosinophils, in addition to further increases of the typical changes induced by DE. OA treatment induced OA-specific IgG1 and IgE production in plasma, whereas the adjuvant effects of DE exposure on immunoglobulin production were not observed. Inhalation of DE led to increased levels of IL-5 protein in the lung at a soot concentration of 1.0 and 3.0 mg/m3 with OA, although these increases did not reach statistical significance. We conclude that the combination of antigen and chronic exposure to DE produces increased eosinophilic inflammation, and cell damage to the epithelium may depend on the degree of eosinophilic inflammation in the airway.
Ichinose
T
T
Research Team for Health Effects of Air Pollutants, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
Takano
H
H
Miyabara
Y
Y
Sagai
M
M
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology; D001335:Vehicle Emissions / Q000633:toxicity*
D016207:Cytokines; D007074:Immunoglobulin G; D001335:Vehicle Emissions; D007073:Immunoglobulin E; D010047:Ovalbumin