title: Murine precision-cut lung slices exhibit acute responses following exposure to gasoline direct injection engine emissions.
abstract: Gasoline direct injection (GDI) engines are increasingly prevalent in the global vehicle fleet. Particulate matter emissions from GDI engines are elevated compared to conventional gasoline engines. The pulmonary effects of these higher particulate emissions are unclear. This study investigated the pulmonary responses induced by GDI engine exhaust using an ex vivo model. The physiochemical properties of GDI engine exhaust were assessed. Precision cut lung slices were prepared using Balb/c mice to evaluate the pulmonary response induced by one-hour exposure to engine-out exhaust from a laboratory GDI engine operated at conditions equivalent to vehicle highway cruise conditions. Lung slices were exposed at an air-liquid interface using an electrostatic aerosol in vitro exposure system. Particulate and gaseous exhaust was fractionated to contrast mRNA production related to polycyclic aromatic hydrocarbon (PAH) metabolism and oxidative stress. Exposure to GDI engine exhaust upregulated genes involved in PAH metabolism, including Cyp1a1 (2.71, SE=0.22), and Cyp1b1 (3.24, SE=0.12) compared to HEPA filtered air (p<0.05). GDI engine exhaust further increased Cyp1b1 expression compared to filtered GDI engine exhaust (i.e., gas fraction only), suggesting this response was associated with the particulate fraction. Exhaust particulate was dominated by high molecular weight PAHs. Hmox1, an oxidative stress marker, exhibited increased expression after exposure to GDI (1.63, SE=0.03) and filtered GDI (1.55, SE=0.04) engine exhaust compared to HEPA filtered air (p<0.05), likely attributable to a combination of the gas and particulate fractions. Exposure to GDI engine exhaust contributes to upregulation of genes related to the metabolism of PAHs and oxidative stress.
authors.affiliation: Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, 01003, USA; Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, M5S 3E5, Canada.
authors.forename: Caitlin L
authors.initials: CL
authors.lastname: Maikawa
authors.affiliation: Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, M5S 3E5, Canada; Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, M5S 3G8, Canada.
authors.forename: Naomi
authors.initials: N
authors.lastname: Zimmerman
authors.affiliation: Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, M5S 3G8, Canada.
authors.forename: Khaled
authors.initials: K
authors.lastname: Rais
authors.affiliation: Institute of Musculoskeletal Sciences, University College London, Brockley Hill, Stanmore, London HA7 4LP, United Kingdom.
authors.forename: Mittal
authors.initials: M
authors.lastname: Shah
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA; Respiratory Health Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.
authors.forename: Brie
authors.initials: B
authors.lastname: Hawley
authors.affiliation: Division of Environmental Health & Risk Management, School of Geography, Earth & Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Pant
authors.affiliation: Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, M5S 3E5, Canada.
authors.forename: Cheol-Heon
authors.initials: CH
authors.lastname: Jeong
authors.affiliation: Division of Environmental Health & Risk Management, School of Geography, Earth & Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.
authors.forename: Juana Maria
authors.initials: JM
authors.lastname: Delgado-Saborit
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA; Department of Mechanical Engineering, Colorado State University, Fort Collins, CO 80521, USA.
authors.forename: John
authors.initials: J
authors.lastname: Volckens
authors.affiliation: Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, M5S 3E5, Canada.
authors.forename: Greg
authors.initials: G
authors.lastname: Evans
authors.affiliation: Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, M5S 3G8, Canada.
authors.forename: James S
authors.initials: JS
authors.lastname: Wallace
authors.affiliation: Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, 01003, USA. Electronic address: kpollitt@umass.edu.
authors.forename: Krystal J
authors.initials: KJ
authors.lastname: Godri Pollitt
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005742:Gasoline / Q000633:toxicity*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D052638:Particulate Matter / Q000633:toxicity*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D005742:Gasoline; D008565:Membrane Proteins; D052638:Particulate Matter; D001335:Vehicle Emissions; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Cyp1b1; Gasoline direct injection engine exhaust; Hmox1; Inflammation; Polycyclic aromatic hydrocarbons; Precision-cut lung slices