title: Toxicity of aged gasoline exhaust particles to normal and diseased airway epithelia.
abstract: Particulate matter (PM) pollution is a leading cause of premature death, particularly in those with pre-existing lung disease. A causative link between particle properties and adverse health effects remains unestablished mainly due to complex and variable physico-chemical PM parameters. Controlled laboratory experiments are required. Generating atmospherically realistic aerosols and performing cell-exposure studies at relevant particle-doses are challenging. Here we examine gasoline-exhaust particle toxicity from a Euro-5 passenger car in a uniquely realistic exposure scenario, combining a smog chamber simulating atmospheric ageing, an aerosol enrichment system varying particle number concentration independent of particle chemistry, and an aerosol deposition chamber physiologically delivering particles on air-liquid interface (ALI) cultures reproducing normal and susceptible health status. Gasoline-exhaust is an important PM source with largely unknown health effects. We investigated acute responses of fully-differentiated normal, distressed (antibiotics-treated) normal, and cystic fibrosis human bronchial epithelia (HBE), and a proliferating, single-cell type bronchial epithelial cell-line (BEAS-2B). We show that a single, short-term exposure to realistic doses of atmospherically-aged gasoline-exhaust particles impairs epithelial key-defence mechanisms, rendering it more vulnerable to subsequent hazards. We establish dose-response curves at realistic particle-concentration levels. Significant differences between cell models suggest the use of fully-differentiated HBE is most appropriate in future toxicity studies.
authors.affiliation: Institute of Anatomy, University of Bern, 3012 Bern, Switzerland.
authors.forename: Lisa
authors.initials: L
authors.lastname: Künzi
authors.affiliation: Laboratory of Atmospheric Chemistry, Paul Scherrer Institute (PSI), 5232 Villigen, Switzerland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Krapf
authors.affiliation: Department of Civil and Environmental Engineering, University of Southern California, Los Angeles, CA 90089, United States of America.
authors.forename: Nancy
authors.initials: N
authors.lastname: Daher
authors.affiliation: Laboratory of Atmospheric Chemistry, Paul Scherrer Institute (PSI), 5232 Villigen, Switzerland.
authors.forename: Josef
authors.initials: J
authors.lastname: Dommen
authors.affiliation: Institute of Anatomy, University of Bern, 3012 Bern, Switzerland.
authors.forename: Natalie
authors.initials: N
authors.lastname: Jeannet
authors.affiliation: Institute of Anatomy, University of Bern, 3012 Bern, Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Laboratory of Atmospheric Chemistry, Paul Scherrer Institute (PSI), 5232 Villigen, Switzerland.
authors.forename: Stephen
authors.initials: S
authors.lastname: Platt
authors.affiliation: Laboratory of Atmospheric Chemistry, Paul Scherrer Institute (PSI), 5232 Villigen, Switzerland.
authors.forename: Jay G
authors.initials: JG
authors.lastname: Slowik
authors.affiliation: Division of Pulmonary, Critical Care &Sleep Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Baumlin
authors.affiliation: Division of Pulmonary, Critical Care &Sleep Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Salathe
authors.affiliation: Laboratory of Atmospheric Chemistry, Paul Scherrer Institute (PSI), 5232 Villigen, Switzerland.
authors.forename: André S H
authors.initials: AS
authors.lastname: Prévôt
authors.affiliation: Centre for Atmospheric Sciences, Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
authors.forename: Markus
authors.initials: M
authors.lastname: Kalberer
authors.affiliation: Department of Mathematics and Statistics, Institute of Mathematical Statistics and Actuarial Science, University of Bern, 3012 Bern, Switzerland.
authors.forename: Christof
authors.initials: C
authors.lastname: Strähl
authors.affiliation: Department of Mathematics and Statistics, Institute of Mathematical Statistics and Actuarial Science, University of Bern, 3012 Bern, Switzerland.
authors.forename: Lutz
authors.initials: L
authors.lastname: Dümbgen
authors.affiliation: Department of Civil and Environmental Engineering, University of Southern California, Los Angeles, CA 90089, United States of America.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
authors.affiliation: Laboratory of Atmospheric Chemistry, Paul Scherrer Institute (PSI), 5232 Villigen, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Baltensperger
authors.affiliation: Institute of Anatomy, University of Bern, 3012 Bern, Switzerland.
authors.forename: Marianne
authors.initials: M
authors.lastname: Geiser
mesh_terms: D000336:Aerosols / Q000032:analysis; D000393:Air Pollutants / Q000032:analysis; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005742:Gasoline / Q000032:analysis*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D010316:Particle Size; D052638:Particulate Matter / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D001335:Vehicle Emissions / Q000032:analysis*
chemical_list: D000336:Aerosols; D000393:Air Pollutants; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D005742:Gasoline; D015850:Interleukin-6; D016209:Interleukin-8; D052638:Particulate Matter; D001335:Vehicle Emissions