Research
Effects of ultrafine particles-induced oxidative stress on Clara cells in allergic lung inflammation
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* Corresponding author: Francesca Alessandrini franci@helmholtz-muenchen.de
1 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, ZAUM Center for Allergy and Environment, Biedersteinerstrasse 29, 80802 Munich, Germany
2 Focus Network Nanoparticles and Health (NanoHealth), Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany
3 Laboratory of Toxicology and Applied Pharmacology, Faculty of Medicine, Catholic University of Louvain, 53.02 Avenue E. Mounier, B-1200 Brussels, Belgium
4 Institute of Lung Biology and Disease, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany
5 Institute of Ecological Chemistry, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany
Particle and Fibre Toxicology 2010, 7:11 doi:10.1186/1743-8977-7-11
Published: 26 April 2010Abstract
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 μg/m3 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-α 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-α 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.
Conclusion
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.