Frontiers in Immunology
| العنوان: | Frontiers in Immunology |
|---|---|
| المؤلفون: | Dylan K. McDaniel, Veronica M. Ringel-Scaia, Holly A. Morrison, Sheryl Coutermarsh-Ott, McAlister Council-Troche, Jonathan W. Angle, Justin B. Perry, Grace Davis, Weinan Leng, Valerie Minarchick, Yi Yang, Bo Chen, Sky W. Reece, David A. Brown, Thomas E. Cecere, Jared M. Brown, Kymberly M. Gowdy, Michael F. Hochella, Irving C. Allen |
| المساهمون: | Biomedical Sciences and Pathobiology, Geosciences, Human Nutrition, Foods, and Exercise, Institute for Critical Technology and Applied Science, Materials Science and Engineering, Virginia-Maryland College of Veterinary Medicine |
| المصدر: | Frontiers in Immunology, Vol 10 (2019) Frontiers in Immunology |
| بيانات النشر: | Frontiers, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Cytotoxicity, Immunologic, Male, 0301 basic medicine, air pollution, environmental exposure, Apoptosis, medicine.disease_cause, Mice, 0302 clinical medicine, Airway resistance, Immunology and Allergy, Macrophage, Respiratory system, Lung, Original Research, Membrane Potential, Mitochondrial, Titanium, chemistry.chemical_classification, nanoparticle, TixO2x−1, Environmental exposure, respiratory system, Respiratory Function Tests, 3. Good health, Cell biology, in vivo, Cytokines, cytotoxicity, Disease Susceptibility, Signal Transduction, lcsh:Immunologic diseases. Allergy, Programmed cell death, Immunology, Lung injury, 03 medical and health sciences, medicine, Animals, Humans, Reactive oxygen species, L-Lactate Dehydrogenase, Gene Expression Profiling, Macrophages, 030104 developmental biology, chemistry, 13. Climate action, Reactive Oxygen Species, lcsh:RC581-607, Biomarkers, Oxidative stress, 030215 immunology |
| الوصف: | 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. This 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). |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3140f662d46cc872f2c07ea9b85ce2bcTest https://hdl.handle.net/10919/96682Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3140f662d46cc872f2c07ea9b85ce2bc |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |