title: Effects of ultrafine particles-induced oxidative stress on Clara cells in allergic lung inflammation.
abstract: BACKGROUND
  Clara cell protein (CC16), the main secretory product of bronchiolar Clara cells, plays an important protective role in the respiratory tract against oxidative stress and inflammation. The purpose of the study was to investigate the role of elemental carbon ultrafine particles (EC-UFP)-induced oxidative stress on Clara cells and CC16 in a mouse model of allergic lung inflammation.
  
  
  METHODS
  Ovalbumin (OVA)-sensitized mice were exposed to EC-UFP (507 microg/m(3) for 24 h) or filtered air immediately prior to allergen challenge and systemically treated with N-acetylcysteine (NAC) or vehicle prior and during EC-UFP inhalation. CC16 was measured up to one week after allergen challenge in bronchoalveolar lavage fluid (BALF) and in serum. The relative expression of CC16 and TNF-alpha mRNA were measured in lung homogenates. A morphometrical analysis of mucus hypersecretion and electron microscopy served to investigate goblet cell metaplasia and Clara cell morphological alterations.
  
  
  RESULTS
  In non sensitized mice EC-UFP inhalation caused alterations in CC16 concentration, both at protein and mRNA level, and induced Clara cell hyperplasia. In sensitized mice, inhalation of EC-UFP prior to OVA challenge caused most significant alterations of BALF and serum CC16 concentration, BALF total protein and TNF-alpha relative expression compared to relevant controls; their Clara cells displayed the strongest morphological alterations and strongest goblet cell metaplasia occurred in the small airways. NAC strongly reduced both functional and morphological alterations of Clara cells.
  
  
  CONCLUSIONS
  Our findings demonstrate that oxidative stress plays an important role in EC-UFP-induced augmentation of functional and morphological alterations of Clara cells in allergic lung inflammation.
authors.affiliation: Division of Environmental Dermatology and Allergy, Helmholtz Zentrum/Technische Universität München, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany. franci@helmholtz-muenchen.de
authors.forename: Francesca
authors.initials: F
authors.lastname: Alessandrini
authors.forename: Ingrid
authors.initials: I
authors.lastname: Weichenmeier
authors.forename: Erik
authors.initials: E
authors.lastname: van Miert
authors.forename: Shinji
authors.initials: S
authors.lastname: Takenaka
authors.forename: Erwin
authors.initials: E
authors.lastname: Karg
authors.forename: Cornelia
authors.initials: C
authors.lastname: Blume
authors.forename: Martin
authors.initials: M
authors.lastname: Mempel
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
authors.forename: Alfred
authors.initials: A
authors.lastname: Bernard
authors.forename: Heidrun
authors.initials: H
authors.lastname: Behrendt
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects* / Q000276:immunology; D052638:Particulate Matter / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014598:Uteroglobin / Q000235:genetics / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; C556390:Scgb1a1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D010047:Ovalbumin; D014598:Uteroglobin