AAAR 36th Annual Conference October 16 - October 20, 2017 Raleigh Convention Center Raleigh, North Carolina, USA
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Investigation of Combustion Aerosol Toxicity within the HICE-Project: Chemical Composition of Different Combustion-Emissions and Their Molecular Biological Effects on Air/Liquid-Interface Exposed Lung Cells (In-Vitro) as Well as on Exposed Mice (In-Vivo)
RALF ZIMMERMANN, Gunnar Dittmar, Tamara Kanashova, Jeroen Buters, Sebastian Öder, Hanns Paur, Marco Dilger, Carsten Weiss, Bert Buchholz, Benjamin Stengel, Karsten Hiller, Sean Sapcariu, Kelly BeruBe, Tobias Krebs, Thorsten Streibel, Jürgen Schnelle-Kreis, Martin Sklorz, Johannes Passig, Jürgen Orasche, Pasi Jalava, Mikko Happo, Maija-Riitta Hirvonen, Olli Sipppula, Jorma Jokiniemi, HICE Consortium, Helmholtz Zentrum München and Rostock University
Abstract Number: 259 Working Group: Health Related Aerosols
Abstract Combustion aerosol emissions are important for health effects. The acute response of lung cells onto combustion aerosols include e.g. oxidative stress, inflammation or apoptosis. Only few links between aerosol chemical composition and biological effects have been established yet. In the framework of the Virtual Helmholtz Institute-HICE (www.hice-vi.eu), physical and chemical properties of combustion emissions as well as their biological effects on lung cells (human epithelial cells, A549, BEAS2B, primary cells and murine macrophages, RAW) are jointly analysed. Partly animals were exposed (BL6 mice) for validation purposes. Chemical composition and physical parameters of the emissions were thoroughly characterized. For addressing the biological activity/toxicity of the aerosols, the lung cell-cultures were realistically exposed by novel air-liquid interface (ALI) exposure-systems. After 4h exposure biological effects were analysed by multi-omics characterisation (transcriptomic, proteomic and metabolomics level). Emissions of wood-pellet- and log wood-stoves, ship engines, car diesel- and gasoline-engines were investigated by this approach using two field-deployable ALI-exposure-station systems and a mobile S2-bio safety laboratory. After exposure biological effects were comprehensively characterized (viability, cytotoxicology, multi-omics) and are put in context with the chemical and physical aerosol data [Oeder etal., PLoSone2015, DOI:10.1371/journal.pone.0126536]. Interestingly, the observed biological response-strength differs considerably for different aerosol sources and is not correlated to the deposited PM2.5-mass. This points towards large differences in the relative toxicity of the aerosol emissions from different combustion sources and fuel types. Furthermore adverse and protective effects are observed for different compounds. For example, well burnt-out, low-PM2.5 pellet-burner emission cause higher adverse biological effects than organic-rich, high-PM2.5 logwood stove-emissions. The high abundance of antioxidant compounds such polyphenols in the logwood stove-emissions likely explains this counter-intuitive observation. The latter findings are supported by detailed analyses of activated cellular response pathways (GO-term analysis), depicting regulation of pathways such as pro-inflammatory signalling, xenobiotic metabolism, phagocytosis or oxidative stress and findings from the animal exposure experiments. Further experiments included e.g. exposures with simulated atmospherically-aged emissions (UV-aging in flow tube).