Nitrogen dioxide enhances allergic airway inflammation and hyperresponsiveness in the mouse.
In addition to being an air pollutant, 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 ppm NO2 for 3 days or 5 days followed by a 20-day recovery period. Whereas 5 ppm NO2 elicited no pathological changes, inhalation of 25 ppm NO2 alone induced acute lung injury, which peaked after 3 days and was characterized by increases in protein, LDH, and neutrophils recovered by BAL, as well as lesions within terminal bronchioles. Importantly, 25 ppm NO2 was also sufficient to cause AHR in mice, a cardinal feature of asthma. The inflammatory changes were ameliorated after 5 days of inhalation and completely resolved after 20 days of recovery after the 5-day inhalation. In contrast, in mice immunized and challenged with OVA, inhalation of 25 ppm NO2 caused a marked augmentation of eosinophilic inflammation and terminal bronchiolar lesions, which extended significantly into the alveoli. Moreover, 20 days postcessation of the 5-day 25 ppm NO2 inhalation regimen, eosinophilic and neutrophilic inflammation, pulmonary lesions, and AHR were still present in mice immunized and challenged with OVA. Collectively, these observations suggest an important role for NO2 in airway pathologies associated with asthma, both in modulation of degree and duration of inflammatory response, as well as in induction of AHR.
Poynter
Matthew E
ME
Department of Medicine, University of Vermont, Burlington, VT 05405, USA.
Persinger
Rebecca L
RL
Irvin
Charles G
CG
Butnor
Kelly J
KJ
van Hirtum
Hans
H
Blay
Wendy
W
Heintz
Nicholas H
NH
Robbins
Justin
J
Hemenway
David
D
Taatjes
Douglas J
DJ
Janssen-Heininger
Yvonne
Y
D000818:Animals; D001980:Bronchi / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006967:Hypersensitivity / Q000150:complications* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009585:Nitrogen Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D010083:Oxidants, Photochemical / Q000008:administration & dosage / Q000494:pharmacology*; D011014:Pneumonia / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*
D010083:Oxidants, Photochemical; D010047:Ovalbumin; D009585:Nitrogen Dioxide