Diesel exhaust particles exert acute effects on airway inflammation and function in murine allergen provocation models
Background: Epidemiologic studies show that sudden surges in ambient particulate matter (PM) levels can trigger acute asthma exacerbations. Although diesel exhaust particles (DEPs) act as an adjuvant for allergic sensitization, this is a delayed response and does not explain acute PM effects on airway hyperreactivity (AHR). Objective: Our aim was to determine the acute effects of DEPs on AHR using a mouse model. Methods: Three protocols were developed, 2 of which require OVA sensitization, whereas the third was OVA independent. In the mild sensitization protocol BALB/c mice receive intraperitoneal OVA without alum and are then challenged with aerosolized OVA with or without DEPs. In the postchallenge model DEPs are delivered after OVA challenge to animals sensitized by intraperitoneal OVA plus alum. In the third protocol nebulizer DEPs were also delivered to IL-5-overexpressing mice that exhibit constitutive airway inflammation. Animals were subjected to whole-body plethysmography (WBP) and then killed for performance of bronchoalveolar lavage, histology, and serology. Results: DEP delivery concomitant with OVA challenge or after the induction of airway inflammation with this allergen induced increased AHR in models 1 and 2, respectively. Although these animals showed DEP-induced inflammation and mucus production in the intermediary airways, there was no effect on OVA-specific IgE or TH2 cytokine production. In the IL-5 transgenic mice it was possible to induce similar effects with DEPs in the absence of an allergen. Conclusion: We demonstrate that DEPs induced AHR independent of their adjuvant effects, suggesting the use of these models to study the mechanism or mechanisms of acute asthma exacerbation by means of PM.
Publication Source (Journal or Book title)
Journal of Allergy and Clinical Immunology
Hao, M., Comier, S., Wang, M., Lee, J., & Nel, A. (2003). Diesel exhaust particles exert acute effects on airway inflammation and function in murine allergen provocation models. Journal of Allergy and Clinical Immunology, 112 (5), 905-914. https://doi.org/10.1016/j.jaci.2003.07.005