Role of Oxidative Stress in Ultrafine Particle-Induced Exacerbation of Allergic Lung Inflammation.
http://www.ncbi.nlm.nih.gov/pubmed/19264975?ordinalpos=3&itool=Email.EmailReport.Pubmed_ReportSelector.Pubmed_RVDocSum
Division of Environmental Dermatology and Allergy , Helmholtz Zentrum/Technische Universitat Munchen, ZAUM Center for Allergy and Environment, Neuherberg and Munich, Germany; Focus Network Nanoparticles and Health (NanoHealth) , Helmholtz Zentrum Munchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
RATIONALE: The effects of ultrafine particles inhalation on allergic airway inflammation is of growing interest. The mechanisms underlying these effects are currently under investigation. OBJECTIVES: To investigate the role of oxidative stress on the adjuvant activity of inhaled elemental carbon ultrafine particles (EC-UFP) on allergic airway inflammation. METHODS: Ovalbumin-sensitized mice were exposed to EC-UFP(504microHg/m(3) for 24 h) or filtered air immediately prior to allergen challenge and systemically treated with Nacetylcysteine or vehicle prior and during EC-UFP inhalation. Allergic inflammation was measured up to one 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 ECUFP in lung tissue and both EMSA and immunohistochemistry to quantify/localize NF-kappaB activation. MAIN 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-UFP were detected. N-acetylcysteine treatment significantly reduced the adjuvant activity of EC-UFP. In non sensitized 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-UFP.
PMID: 19264975 [PubMed - as supplied by publisher]
