Role of oxidative stress in ultrafine particle-induced exacerbation of allergic lung inflammation.
BACKGROUND
The effects of ultrafine particle inhalation on allergic airway inflammation are of growing interest. The mechanisms underlying these effects are currently under investigation.


OBJECTIVE
To investigate the role of oxidative stress on the adjuvant activity of inhaled elemental carbon ultrafine particles (EC-UFPs) on allergic airway inflammation.


METHODS
Ovalbumin-sensitized mice were exposed to EC-UFPs (504 microg/m(3) for 24 h) or filtered air immediately before allergen challenge and systemically treated with N-acetylcysteine or vehicle before and during EC-UFP inhalation. Allergic inflammation was measured up to 1 week after allergen challenge by means of bronchoalveolar lavage, cytokine/total protein assays, lung function, and histology. Isoprostane levels in lung tissue served to measure oxidative stress. Transmission electron microscopy served to localize EC-UFPs in lung tissue and both electrophoretic mobility shift assay and immunohistochemistry to quantify/localize nuclear factor-kappaB (NF-kappaB) activation.


RESULTS
In sensitized and challenged mice EC-UFP inhalation increased allergen-induced lung lipid peroxidation and NF-kappaB activation in addition to inflammatory infiltrate, cytokine release, and airway hyperresponsiveness. Prominent NF-kappaB activation was observed in the same cell types in which EC-UFPs were detected. N-acetylcysteine treatment significantly reduced the adjuvant activity of EC-UFPs. In nonsensitized or sensitized but not challenged mice EC-UFP exposure induced a moderate increase in isoprostanes but no significant effect on other parameters of lung inflammation.


CONCLUSIONS
Our findings demonstrate a critical role for oxidative stress in EC-UFP-induced augmentation of allergen-induced lung inflammation, where EC-UFP exposure has potentiating effects in lung allergic inflammation. Our data support the concept that allergic individuals are more susceptible to the adverse health effects of EC-UFPs.
Alessandrini
Francesca
F
Division of Environmental Dermatology and Allergy, Helmholtz Zentrum/Technische Universität München, ZAUM Center for Allergy and Environment, Helmholtz Zentrum München, Neuherberg, Germany. franci@helmholtz-muenchen.de
Beck-Speier
Ingrid
I
Krappmann
Daniel
D
Weichenmeier
Ingrid
I
Takenaka
Shinji
S
Karg
Erwin
E
Kloo
Bernhard
B
Schulz
Holger
H
Jakob
Thilo
T
Mempel
Martin
M
Behrendt
Heidrun
H
D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000473:pathology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines; D005260:Female; D006967:Hypersensitivity / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D019570:Inhalation Exposure / Q000009:adverse effects; D015227:Lipid Peroxidation; D051379:Mice; D016328:NF-kappa B; D018384:Oxidative Stress / Q000276:immunology*; D052638:Particulate Matter / Q000009:adverse effects*
D000393:Air Pollutants; D016207:Cytokines; D016328:NF-kappa B; D052638:Particulate Matter