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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02714

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

Dylan K. McDaniel1,  Veronica M. Ringel-Scaia1,  Sheryl Coutermarsh-Ott1,  McAlister Council-Troche1, Jonathan W. Angle1, Justin B. Perry1, Grace Davis1,  Weinan Leng Leng1,  Valerie Minarchick2, Yi Yang3, Bo Chen4,  Sky W. Reece5, David A. Brown1,  Thomas Cecere1,  Jared Brown2,  Kymberly M. Gowdy5, Michael F. Hochella Jr1 and  Irving C. Allen1*
  • 1Virginia Tech, United States
  • 2University of Colorado Anschutz Medical Campus, United States
  • 3East China Normal University, China
  • 4University of North Carolina at Chapel Hill, United States
  • 5East Carolina University, United States

Coal 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 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.

Keywords: Cytotoxicity, Air Pollution, nanoparticle, TixO2x-1, in vivo, Environmental Exposure

Received: 16 Jul 2019; Accepted: 05 Nov 2019.

Copyright: © 2019 McDaniel, Ringel-Scaia, Coutermarsh-Ott, Council-Troche, Angle, Perry, Davis, Leng, Minarchick, Yang, Chen, Reece, Brown, Cecere, Brown, Gowdy, Hochella Jr and Allen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Irving C. Allen, Virginia Tech, Blacksburg, 24061, Virginia, United States,