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Metabolic profiling as well as stable isotope assisted metabolic and proteomic analysis of RAW 264.7 macrophages exposed to ship engine aerosol emissions: different effects of heavy fuel Oil and refined diesel fuel

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Item Type:Article
Title:Metabolic profiling as well as stable isotope assisted metabolic and proteomic analysis of RAW 264.7 macrophages exposed to ship engine aerosol emissions: different effects of heavy fuel Oil and refined diesel fuel
Creators Name:Sapcariu, S.C. and Kanashova, T. and Dilger, M. and Diabate, S. and Oeder, S. and Passig, J. and Radischat, C. and Buters, J. and Sippula, O. and Streibel, T. and Paur, H.R. and Schlager, C. and Muelhopt, S. and Stengel, B. and Rabe, R. and Harndorf, H. and Krebs, T. and Karg, E. and Groeger, T. and Weiss, C. and Dittmar, G. and Hiller, K. and Zimmermann, R.
Abstract:Exposure to air pollution resulting from fossil fuel combustion has been linked to multiple short-term and long term health effects. In a previous study, exposure of lung epithelial cells to engine exhaust from heavy fuel oil (HFO) and diesel fuel (DF), two of the main fuels used in marine engines, led to an increased regulation of several pathways associated with adverse cellular effects, including pro-inflammatory pathways. In addition, DF exhaust exposure was shown to have a wider response on multiple cellular regulatory levels compared to HFO emissions, suggesting a potentially higher toxicity of DF emissions over HFO. In order to further understand these effects, as well as to validate these findings in another cell line, we investigated macrophages under the same conditions as a more inflammation-relevant model. An air-liquid interface aerosol exposure system was used to provide a more biologically relevant exposure system compared to submerged experiments, with cells exposed to either the complete aerosol (particle and gas phase), or the gas phase only (with particles filtered out). Data from cytotoxicity assays were integrated with metabolomics and proteomics analyses, including stable isotope-assisted metabolomics, in order to uncover pathways affected by combustion aerosol exposure in macrophages. Through this approach, we determined differing phenotypic effects associated with the different components of aerosol. The particle phase of diluted combustion aerosols was found to induce increased cell death in macrophages, while the gas phase was found more to affect the metabolic profile. In particular, a higher cytotoxicity of DF aerosol emission was observed in relation to the HFO aerosol. Furthermore, macrophage exposure to the gas phase of HFO leads to an induction of a pro-inflammatory metabolic and proteomic phenotype. These results validate the effects found in lung epithelial cells, confirming the role of inflammation and cellular stress in the response to combustion aerosols.
Keywords:Cell Line, Fuel Oils, Gasoline, Macrophages, Metabolome, Proteome, Vehicle Emissions, Animals, Mice
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science (U.S.A.)
Volume:11
Number:6
Page Range:e0157964
Date:27 June 2016
Official Publication:https://doi.org/10.1371/journal.pone.0157964
PubMed:View item in PubMed

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