ZFIN ID: ZDB-PUB-191219-10
Pulmonary Exposure to Magnéli Phase Titanium Suboxides Results in Significant Macrophage Abnormalities and Decreased Lung Function
McDaniel, D.K., Ringel-Scaia, V.M., Morrison, H.A., Coutermarsh-Ott, S., Council-Troche, M., Angle, J.W., Perry, J.B., Davis, G., Leng, W., Minarchick, V., Yang, Y., Chen, B., Reece, S.W., Brown, D.A., Cecere, T.E., Brown, J.M., Gowdy, K.M., Hochella, M.F., Allen, I.C.
Date: 2019
Source: Frontiers in immunology   10: 2714 (Journal)
Registered Authors: Brown, David A.
Keywords: TixO2x−1, air pollution, cytotoxicity, environmental exposure, in vivo, nanoparticle
MeSH Terms:
  • Animals
  • Apoptosis/genetics
  • Apoptosis/immunology
  • Biomarkers
  • Cytokines/metabolism
  • Cytotoxicity, Immunologic
  • Disease Susceptibility
  • Environmental Exposure*
  • Gene Expression Profiling
  • Humans
  • L-Lactate Dehydrogenase/metabolism
  • Lung/drug effects*
  • Lung/metabolism
  • Lung/pathology*
  • Lung/physiopathology
  • Macrophages/immunology
  • Macrophages/metabolism*
  • Macrophages/pathology
  • Male
  • Membrane Potential, Mitochondrial
  • Mice
  • Reactive Oxygen Species/metabolism
  • Respiratory Function Tests
  • Signal Transduction
  • Titanium/adverse effects*
PubMed: 31849940 Full text @ Front Immunol
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 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.