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 investig ated. The relationship between the histopathologic appearances in the airway and immunoglobulin production or local cytokine levels in the l ungs was also studied. ICR mice were exposed to clean air or DE at a s oot concentrations of 0.3, 1.0, or 3.0 mg/m(3) for 34 weeks. Fifteen w eeks after exposure to DE, mice were sensitized intraperitoneally with 10 mu g of OA and challenged by an aerosol of 1% OA six times at S-we ek intervals during the last 18 weeks of the exposure. DE exposure cau sed a dose-dependent increase of nonciliated cell proliferation and ep ithelial cell hypertrophy in the airway, but showed no effect on goble t cell proliferation in the bronchial epithelium and eosinophil recrui tment 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 DIE, OA treatment induced OA-specific IgG, and IgE production in plasma, whereas the adjuvant effects of DE expo sure on immunoglobulin production were not observed, Inhalation of DE led to increased levels of IL-5 protein in the lung at a soot concentr ation of 1.0 and 3.0 mg/m(3) with OA, although these increases did not reach statistical significance. We conclude that the combination of a ntigen and chronic exposure to DE produces increased eosinophilic infl ammation, and cell damage to the epithelium may depend on the degree o f eosinophilic inflammation in the airway. (C) 1998 Society of Toxicol ogy.