Nitrogen dioxide promotes allergic sensitization to inhaled antigen.
Allergen sensitization and allergic airway disease are likely to come about through the inhalation of Ag with immunostimulatory molecules. However, environmental pollutants, including nitrogen dioxide (NO2), may promote adaptive immune responses to innocuous Ags that are not by themselves immunostimulatory. We tested in C57BL/6 mice whether exposure to NO2, followed by inhalation of the innocuous protein Ag, OVA, would result in allergen sensitization and the subsequent development of allergic airway disease. Following challenge with aerosolized OVA alone, mice previously exposed via inhalation to NO2 and OVA developed eosinophilic inflammation and mucus cell metaplasia in the lungs, as well as OVA-specific IgE and IgG1, and Th2-type cytokine responses. One hour of exposure to 10 parts per million NO2 increased bronchoalveolar lavage fluid levels of total protein, lactate dehydrogenase activity, and heat shock protein 70; promoted the activation of NF-kappaB by airway epithelial cells; and stimulated the subsequent allergic response to Ag challenge. Furthermore, features of allergic airway disease were not induced in allergen-challenged TLR2-/- and MyD88-/- mice exposed to NO2 and aerosolized OVA during sensitization. These findings offer a mechanism whereby allergen sensitization and asthma may result under conditions of high ambient or endogenous NO2 levels.
Bevelander
Mieke
M
Vermont Lung Center, University of Vermont, Burlington, VT 05405, USA.
Mayette
Jana
J
Whittaker
Laurie A
LA
Paveglio
Sara A
SA
Jones
Christine C
CC
Robbins
Justin
J
Hemenway
David
D
Akira
Shizuo
S
Uematsu
Satoshi
S
Poynter
Matthew E
ME
D000280:Administration, Inhalation; D000336:Aerosols; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology; D004802:Eosinophilia / Q000139:chemically induced / Q000276:immunology; D007155:Immunologic Factors / Q000008:administration & dosage*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008679:Metaplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009093:Mucus / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D009585:Nitrogen Dioxide / Q000008:administration & dosage*; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology