title: Combined exposure of diesel exhaust particles and respirable Soufrière Hills volcanic ash causes a (pro-)inflammatory response in an in vitro multicellular epithelial tissue barrier model.
abstract: There are justifiable health concerns regarding the potential adverse effects associated with human exposure to volcanic ash (VA) particles, especially when considering communities living in urban areas already exposed to heightened air pollution. The aim of this study was, therefore, to gain an imperative, first understanding of the biological impacts of respirable VA when exposed concomitantly with diesel particles.
  
  
  
  A sophisticated in vitro 3D triple cell co-culture model of the human alveolar epithelial tissue barrier was exposed to either a single or repeated dose of dry respirable VA (deposited dose of 0.26 ± 0.09 or 0.89 ± 0.29 μg/cm2, respectively) from Soufrière Hills volcano, Montserrat for a period of 24 h at the air-liquid interface (ALI). Subsequently, co-cultures were exposed to co-exposures of single or repeated VA and diesel exhaust particles (DEP; NIST SRM 2975; 0.02 mg/mL), a model urban pollutant, at the pseudo-ALI. The biological impact of each individual particle type was also analysed under these precise scenarios. The cytotoxic (LDH release), oxidative stress (depletion of intracellular GSH) and (pro-)inflammatory (TNF-α, IL-8 and IL-1β) responses were assessed after the particulate exposures. The impact of VA exposure upon cell morphology, as well as its interaction with the multicellular model, was visualised via confocal laser scanning microscopy (LSM) and scanning electron microscopy (SEM), respectively.
  
  
  
  The combination of respirable VA and DEP, in all scenarios, incited an heightened release of TNF-α and IL-8 as well as significant increases in IL-1β, when applied at sub-lethal doses to the co-culture compared to VA exposure alone. Notably, the augmented (pro-)inflammatory responses observed were not mediated by oxidative stress. LSM supported the quantitative assessment of cytotoxicity, with no changes in cell morphology within the barrier model evident. A direct interaction of the VA with all three cell types of the multicellular system was observed by SEM.
  
  
  
  Combined exposure of respirable Soufrière Hills VA with DEP causes a (pro-)inflammatory effect in an advanced in vitro multicellular model of the epithelial airway barrier. This finding suggests that the combined exposure to volcanic and urban particulate matter should be further investigated in order to deduce the potential human health hazard, especially how it may influence the respiratory function of susceptible individuals (i.e. with pre-existing lung diseases) in the population.
authors.affiliation: Institute of Hazard, Risk and Resilience, Department of Earth Sciences, Durham University, Science Labs, Durham, DH1 3LE, UK. ines.tomasek@durham.ac.uk.|BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, CH-1700, Fribourg, Switzerland. ines.tomasek@durham.ac.uk.
authors.forename: Ines
authors.initials: I
authors.lastname: Tomašek
authors.affiliation: Institute of Hazard, Risk and Resilience, Department of Earth Sciences, Durham University, Science Labs, Durham, DH1 3LE, UK.
authors.forename: Claire J
authors.initials: CJ
authors.lastname: Horwell
authors.affiliation: Department of Earth and Environmental Sciences, Section for Mineralogy, Petrology and Geochemistry, Ludwig-Maximilians-Universität München, Theresienstrasse 41, 80333, Munich, Germany.|United States Geological Survey, 345 Middlefield Road, Menlo Park, CA, 94025, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Damby
authors.affiliation: BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, CH-1700, Fribourg, Switzerland.
authors.forename: Hana
authors.initials: H
authors.lastname: Barošová
authors.affiliation: BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, CH-1700, Fribourg, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Geers
authors.affiliation: BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, CH-1700, Fribourg, Switzerland.|Chemistry Department, University of Fribourg, Chemin des Musee, CH-1700, Fribourg, Switzerland.
authors.forename: Alke
authors.initials: A
authors.lastname: Petri-Fink
authors.affiliation: BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, CH-1700, Fribourg, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rothen-Rutishauser
authors.affiliation: BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, CH-1700, Fribourg, Switzerland. m.j.d.clift@swansea.ac.uk.|In Vitro Toxicology Group, Institute of Life Sciences, Swansea University Medical School, Singleton Park Campus, Swansea, SA2 8PP, Wales, UK. m.j.d.clift@swansea.ac.uk.
authors.forename: Martin J D
authors.initials: MJ
authors.lastname: Clift
mesh_terms: D018920:Coculture Techniques; D004781:Environmental Exposure; D006801:Humans; D066298:In Vitro Techniques; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects*; D001335:Vehicle Emissions / Q000633:toxicity*; D018707:Volcanic Eruptions
chemical_list: D001335:Vehicle Emissions
keywords: (pro-)inflammatory cytokines/chemokines; Air-liquid Interface Exposures; Diesel exhaust particles; In vitro; Multicellular Human Epithelial Tissue Barrier System; Particle co-exposures; Volcanic ash