TY - JOUR
T1 - Metabolic profiling as well as stable isotope assisted metabolic and proteomic analysis of RAW 264.7 macrophages exposed to ship engine aerosol emissions
T2 - Different effects of heavy fuel oil and refined diesel fuel
AU - Sapcariu, Sean C.
AU - Kanashova, Tamara
AU - Dilger, Marco
AU - Diabaté, Silvia
AU - Oeder, Sebastian
AU - Passig, Johannes
AU - Radischat, Christian
AU - Buters, Jeroen
AU - Sippula, Olli
AU - Streibel, Thorsten
AU - Paur, Hanns Rudolf
AU - Schlager, Christoph
AU - Mülhopt, Sonja
AU - Stengel, Benjamin
AU - Rabe, Rom
AU - Harndorf, Horst
AU - Krebs, Tobias
AU - Karg, Erwin
AU - Gröger, Thomas
AU - Weiss, Carsten
AU - Dittmar, Gunnar
AU - Hiller, Karsten
AU - Zimmermann, Ralf
N1 - Publisher Copyright:
© 2016 Sapcariu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/6
Y1 - 2016/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84977470746&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0157964
DO - 10.1371/journal.pone.0157964
M3 - Article
C2 - 27348622
AN - SCOPUS:84977470746
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e0157964
ER -