Role of Oxidative Stress in Ultrafine Particle-induced Exacerbation of Allergic Lung Inflammation

Rationale: The effects of ultrafine particle inhalation on allergic airway inflammation are of growing interest. The mechanisms underlying these effects are currently under investigation. Objectives: To investigate the role of oxidative stress on the adjuvant activity of inhaled elemental carbon ultrafine particles (EC-UFPs) on allergic airway inflammation. Methods: Ovalbumin-sensitized mice were exposed to EC-UFPs (504 mu g/m(3) for 24 h) or filtered air immediately before allergen challenge and systemically treated with N-acetylcysteine or vehicle before and during EC-UFP inhalation. Allergic inflammation was measured up to 1 week after allergen challenge by means of bronchoalveolar lavage, cytokine/total protein assays, lung function, and histology. Isoprostane levels in lung tissue served to measure oxidative stress. Transmission electron microscopy served to localize ECUFPs in lung tissue and both electrophoretic mobility shift assay and immunohistochemistry to quantify/localize nuclear factor-kappa B (NF-kappa B) activation. Measurements and Main Results: In sensitized and challenged mice EC-UFP inhalation increased allergen-induced lung lipid peroxidation and NF-kappa B activation in addition to inflammatory infiltrate, cytokine release, and airway hyperresponsiveness. Prominent NF-kappa B activation was observed in the same cell types in which EC-UFPs were detected. N-acetylcysteine treatment significantly reduced the adjuvant activity of EC-UFPs. In nonsensitized or sensitized but not challenged mice EC-UFP exposure induced a moderate increase in isoprostanes but no significant effect on other parameters of lung inflammation. Conclusions: Our findings demonstrate a critical role for oxidative stress in EC-UFP-induced augmentation of allergen-induced lung inflammation, where EC-UFP exposure has potentiating effects in lung allergic inflammation. Our data support the concept that allergic individuals are more susceptible to the adverse health effects of EC-UFPs.