title: Environmental impact of multi-wall carbon nanotubes in a novel model of exposure: systemic distribution, macrophage accumulation, and amyloid deposition.
abstract: Carbon nanotubes (CNTs) have been extensively investigated and employed for industrial use because of their peculiar physical properties, which make them ideal for many industrial applications. However, rapid growth of CNT employment raises concerns about the potential risks and toxicities for public health, environment, and workers associated with the manufacture and use of these new materials. Here we investigate the main routes of entry following environmental exposure to multi-wall CNTs (MWCNTs; currently the most widely used in industry). We developed a novel murine model that could represent a surrogate of a workplace exposure to MWCNTs. We traced the localization of MWCNTs and their possible role in inducing an innate immune response, inflammation, macrophage recruitment, and inflammatory conditions. Following environmental exposure of CD1 mice, we observed that MWCNTs rapidly enter and disseminate in the organism, initially accumulating in lungs and brain and later reaching the liver and kidney via the bloodstream. Since recent experimental studies show that CNTs are associated with the aggregation process of proteins associated with neurodegenerative diseases, we investigated whether MWCNTs are able to induce amyloid fibril production and accumulation. Amyloid deposits in spatial association with macrophages and MWCNT aggregates were found in the brain, liver, lungs, and kidneys of exposed animals. Our data suggest that accumulation of MWCNTs in different organs is associated with inflammation and amyloid accumulation. In the brain, where we observed rapid accumulation and amyloid fibril deposition, exposure to MWCNTs might enhance progression of neurodegenerative and other amyloid-related diseases. Our data highlight the conclusion that, in a novel rodent model of exposure, MWCNTs may induce macrophage recruitment, activation, and amyloid deposition, causing potential damage to several organs.
authors.affiliation: Laboratory of Translational Research, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Albini
authors.affiliation: Department of Biotechnologies and Life Sciences, University of Insubria, Varese, Italy ; Scientific and Technology Park, IRCCS MultiMedica, Milano, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Pagani
authors.affiliation: Department of Biotechnologies and Life Sciences, University of Insubria, Varese, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pulze
authors.affiliation: Scientific and Technology Park, IRCCS MultiMedica, Milano, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Bruno
authors.affiliation: Scientific and Technology Park, IRCCS MultiMedica, Milano, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Principi
authors.affiliation: Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy.
authors.forename: Terenzio
authors.initials: T
authors.lastname: Congiu
authors.affiliation: Department of Biotechnologies and Life Sciences, University of Insubria, Varese, Italy ; Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gini
authors.affiliation: Department of Biotechnologies and Life Sciences, University of Insubria, Varese, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Grimaldi
authors.affiliation: Department of Biotechnologies and Life Sciences, University of Insubria, Varese, Italy ; Scientific and Technology Park, IRCCS MultiMedica, Milano, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bassani
authors.affiliation: Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: De Flora
authors.affiliation: Department of Biotechnologies and Life Sciences, University of Insubria, Varese, Italy.
authors.forename: Magda
authors.initials: M
authors.lastname: de Eguileor
authors.affiliation: Department of Biotechnologies and Life Sciences, University of Insubria, Varese, Italy ; Scientific and Technology Park, IRCCS MultiMedica, Milano, Italy.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Noonan
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000187:drug effects; D000818:Animals; D004781:Environmental Exposure / Q000009:adverse effects*; D005455:Fluorescent Antibody Technique; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000682:Amyloid; D037742:Nanotubes, Carbon
keywords: amyloid fibrils; animal model; environmental exposure; inflammation; macrophages; nanoparticles