title: Role of oxidative stress in ultrafine particle-induced exacerbation of allergic lung inflammation.
abstract: 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.
authors.affiliation: 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
authors.forename: Francesca
authors.initials: F
authors.lastname: Alessandrini
authors.forename: Ingrid
authors.initials: I
authors.lastname: Beck-Speier
authors.forename: Daniel
authors.initials: D
authors.lastname: Krappmann
authors.forename: Ingrid
authors.initials: I
authors.lastname: Weichenmeier
authors.forename: Shinji
authors.initials: S
authors.lastname: Takenaka
authors.forename: Erwin
authors.initials: E
authors.lastname: Karg
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kloo
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
authors.forename: Thilo
authors.initials: T
authors.lastname: Jakob
authors.forename: Martin
authors.initials: M
authors.lastname: Mempel
authors.forename: Heidrun
authors.initials: H
authors.lastname: Behrendt
mesh_terms: 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*
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D016328:NF-kappa B; D052638:Particulate Matter