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Pulmonary Exposure to Magnéli Phase Titanium Suboxides Results in Significant Macrophage Abnormalities and Decreased Lung Function

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dc.contributor.authorMcDaniel, Dylan K.en
dc.contributor.authorRingel-Scaia, Veronica M.en
dc.contributor.authorMorrison, Holly A.en
dc.contributor.authorCoutermarsh-Ott, Sherylen
dc.contributor.authorCouncil-Troche, McAlisteren
dc.contributor.authorAngle, Jonathan W.en
dc.contributor.authorPerry, Justin B.en
dc.contributor.authorDavis, Graceen
dc.contributor.authorLeng, Weinanen
dc.contributor.authorMinarchick, Valerieen
dc.contributor.authorYang, Yien
dc.contributor.authorChen, Boen
dc.contributor.authorReece, Sky W.en
dc.contributor.authorBrown, David A.en
dc.contributor.authorCecere, Thomas E.en
dc.contributor.authorBrown, Jared M.en
dc.contributor.authorGowdy, Kymberly M.en
dc.contributor.authorHochella, Michael F. Jr.en
dc.contributor.authorAllen, Irving C.en
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.contributor.departmentGeosciencesen
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.contributor.departmentInstitute for Critical Technology and Applied Scienceen
dc.contributor.departmentMaterials Science and Engineeringen
dc.contributor.departmentVirginia-Maryland College of Veterinary Medicineen
dc.date.accessioned2020-02-03T17:44:48Zen
dc.date.available2020-02-03T17:44:48Zen
dc.date.issued2019-11-28en
dc.description.abstractCoal is one of the most abundant and economic sources for global energy production. However, the burning of coal is widely recognized as a significant contributor to atmospheric particulate matter linked to deleterious respiratory impacts. Recently, we have discovered that burning coal generates large quantities of otherwise rare Magnéli phase titanium suboxides from TiO2 minerals naturally present in coal. These nanoscale Magnéli phases are biologically active without photostimulation and toxic to airway epithelial cells in vitro and to zebrafish in vivo. Here, we sought to determine the clinical and physiological impact of pulmonary exposure to Magnéli phases using mice as mammalian model organisms. Mice were exposed to the most frequently found Magnéli phases, Ti6O11, at 100 parts per million (ppm) via intratracheal administration. Local and systemic titanium concentrations, lung pathology, and changes in airway mechanics were assessed. Additional mechanistic studies were conducted with primary bone marrow derived macrophages. Our results indicate that macrophages are the cell type most impacted by exposure to these nanoscale particles. Following phagocytosis, macrophages fail to properly eliminate Magnéli phases, resulting in increased oxidative stress, mitochondrial dysfunction, and ultimately apoptosis. In the lungs, these nanoparticles become concentrated in macrophages, resulting in a feedback loop of reactive oxygen species production, cell death, and the initiation of gene expression profiles consistent with lung injury within 6 weeks of exposure. Chronic exposure and accumulation of Magnéli phases ultimately results in significantly reduced lung function impacting airway resistance, compliance, and elastance. Together, these studies demonstrate that Magnéli phases are toxic in the mammalian airway and are likely a significant nanoscale environmental pollutant, especially in geographic regions where coal combustion is a major contributor to atmospheric particulate matter.en
dc.description.sponsorshipThis work was financially supported by the Virginia-Maryland College of Veterinary Medicine, the National Natural Science Foundation of China (41522111 and 4176114462), The Center for the Environmental Implications of Nanotechnology (NSF Cooperative Agreement EF-0830093), the Virginia Tech Institute for Critical Technology and Applied Science (ICTAS), the Open Foundation of East China Normal University, the Virginia Tech National Center for Earth and Environmental Nanotechnology Infrastructure (NSF Cooperative Agreement ECCS-1542100), the STAR Fellowship Assistance Agreement no. FP-91780101-1 awarded by the U.S. Environmental Protection Agency (EPA), The National Institutes of Health (R01 ES019311). Student work on this publication was supported by the National Institute of Allergy and Infectious Diseases Animal Model Research for Veterinarians (AMRV) training grant (T32-OD010430) and the American Association of Immunologist Careers in Immunology Fellowship Program (VR-S).en
dc.format.extent20 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMcDaniel DK, Ringel-Scaia VM, Morrison HA, Coutermarsh-Ott S, Council-Troche M, Angle JW, Perry JB, Davis G, Leng W, Minarchick V, Yang Y, Chen B, Reece SW, Brown DA, Cecere TE, Brown JM, Gowdy KM, Hochella MF Jr and Allen IC (2019) Pulmonary Exposure to Magnéli Phase Titanium Suboxides Results in Significant Macrophage Abnormalities and Decreased Lung Function. Front. Immunol. 10:2714. doi: 10.3389/fimmu.2019.02714en
dc.identifier.doihttps://doi.org/10.3389/fimmu.2019.02714en
dc.identifier.urihttp://hdl.handle.net/10919/96682en
dc.identifier.volume10en
dc.language.isoenen
dc.publisherFrontiersen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectcytotoxicityen
dc.subjectair pollutionen
dc.subjectnanoparticleen
dc.subjectTixO2x−1en
dc.subjectin vivoen
dc.subjectenvironmental exposureen
dc.titlePulmonary Exposure to Magnéli Phase Titanium Suboxides Results in Significant Macrophage Abnormalities and Decreased Lung Functionen
dc.title.serialFrontiers in Immunologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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