Running Head: Nitrogen dioxide enhances allergic airway disease Address correspondence to:

Nitrogen dioxide enhances allergic airway disease 2 In addition to being an air pollutant, nitrogen dioxide (NO2) is a potent inflammatory oxidant generated endogenously by myeloperoxidase and eosinophil peroxidase. In these studies, we sought to determine the effects of NO2 exposure on mice with ongoing allergic airway disease pathology. Mice were sensitized and challenged with the antigen, ovalbumin (OVA) to generate airway inflammation and subsequently exposed to 5 or 25 parts per million (ppm) NO2 for 3 days, or 5 days followed by a 20 day recovery period. While 5 ppm NO2 elicited no pathologic changes, inhalation of 25 ppm NO2 alone induced acute lung injury, which peaked after 3 days and was characterized by increases in protein, lactate dehydrogenase (LDH), and neutrophils recovered by bronchoalveolar lavage (BAL), as well as lesions within the terminal bronchioles. Importantly, 25 ppm NO2 was also sufficient to cause airways hyperresponsiveness (AHR) in mice, a cardinal feature of asthma. The inflammatory changes were ameliorated after