Repeated exposure to low-dose diesel exhaust after allergen challenge exaggerates asthmatic responses in mice

• Published in: Clinical Immunology 2006-11, Vol.121 (2), p.227-235
• Main Authors: Matsumoto, Aki, Hiramatsu, Kumiko, Li, Yingji, Azuma, Arata, Kudoh, Shoji, Takizawa, Hajime, Sugawara, Isamu
• Format: Article
• Language: English
• Subjects: Allergens - immunology; Animals; Asthma; Asthma - chemically induced; Asthma - immunology; Asthma - physiopathology; Biological and medical sciences; Bronchial Hyperreactivity - etiology; Bronchial Hyperreactivity - immunology; Bronchoalveolar Lavage Fluid - cytology; Chemokines - metabolism; Cytokines - metabolism; Diesel exhaust; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunopathology; Inhalation Exposure; Low dose; Lung - ultrastructure; Medical sciences; Mice; Mice model; Mice, Inbred BALB C; Ovalbumin; RNA, Messenger - metabolism; Vehicle Emissions - toxicity
• ISSN: 1521-6616; 1521-7035; 1365-2567
• DOI: 10.1016/j.clim.2006.08.003

In conjunction with allergens, diesel exhaust particles act as an adjuvant to enhance IgE responses, inducing expression of cytokines/chemokines and adhesion molecules, and increasing airway hyper-responsiveness (AHR). As most studies were designed to expose animals to diesel exhaust throughout the periods of both sensitization and allergen challenge, it remains unclear whether diesel exhaust (DE) exposure exaggerates airway responses in asthmatic animals. To study effects of exposure to low-dose DE on AHR and allergic airway inflammation in asthmatic mice. BALB/c mice were sensitized by intraperitoneal injection of ovalbumin and challenged by intranasal administration with ovalbumin. They were exposed to low-dose DE for 7 h/day, 5 days/week, for up to 12 weeks. AHR to methacholine was evaluated by whole-body plethysmography as well as bronchoalveolar lavage cell analysis and cytokine gene expression in lungs. Repeated exposure of asthmatic mice to low-dose DE resulted in increased AHR and gene expression of several pro-asthmatic cytokines/chemokines, but these effects rapidly subsided with continued exposure to DE. Repeated exposure to low-dose DE after ovalbumin challenge exaggerates allergic responses in mice, but effects are not prolonged with continuous DE exposure.