Role of oxidative stress in ultrafine particle-induced exacerbation of allergic lung inflammation

Abstract

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 microg/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 EC-UFPs in lung tissue and both electrophoretic mobility shift assay and immunohistochemistry to quantify/localize nuclear factor-kappaB (NF-kappaB) activation.

Measurements and main results: In sensitized and challenged mice EC-UFP inhalation increased allergen-induced lung lipid peroxidation and NF-kappaB activation in addition to inflammatory infiltrate, cytokine release, and airway hyperresponsiveness. Prominent NF-kappaB 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.