Oxidant-Induced Epithelial Alarmin Pathway Mediates Lung Inflammation and Functional Decline Following Ultrafine Carbon and Ozone Inhalation Co-Exposure

Details

• Personal Author:
  Castranova, Vincent ; Erdely A ; Friend SA ; Goldsmith WT ; Harkema JR ; Hussain S ; Kelly EE ; Khramtsov VV ; Kodali VK ; Majumder N ; Nurkiewicz TR ; Velayutham M ; Zeidler-Erdely PC
• Description:
  Environmental inhalation exposures are inherently mixed (gases and particles), yet regulations are still based on single toxicant exposures. While the impacts of individual components of environmental pollution have received substantial attention, the impact of inhalation co-exposures is poorly understood. Here, we mechanistically investigated pulmonary inflammation and lung function decline after inhalation co-exposure and individual exposures to ozone (O3) and ultrafine carbon black (CB). Environmentally/occupationally relevant lung deposition levels in mice were achieved after inhalation of stable aerosols with similar aerodynamic and mass median distributions. X-ray photoemission spectroscopy detected increased surface oxygen contents on particles in co-exposure aerosols. Compared with individual exposures, co-exposure aerosols produced greater acellular and cellular oxidants detected by electron paramagnetic resonance (EPR) spectroscopy, and in vivo immune-spin trapping (IST), as well as synergistically increased lavage neutrophils, lavage proteins and inflammation related gene/protein expression. Co-exposure induced a significantly greater respiratory function decline compared to individual exposure. A synthetic catalase-superoxide dismutase mimetic (EUK-134) significantly blunted lung inflammation and respiratory function decline confirming the role of oxidant imbalance. We identified a significant induction of epithelial alarmin (thymic stromal lymphopoietin-TSLP)-dependent interleukin-13 pathway after co-exposure, associated with increased mucin and interferon gene expression. We provided evidence of interactive outcomes after air pollution constituent co-exposure and identified a key mechanistic pathway that can potentially explain epidemiological observation of lung function decline after an acute peak of air pollution. Developing and studying the co-exposure scenario in a standardized and controlled fashion will enable a better mechanistic understanding of how environmental exposures result in adverse outcomes. [Description provided by NIOSH]
• Subjects:
  Coal Coal Mining Mining Occupational Health Safety
• Keywords:
  Aerosols Author Keywords: EPR Carbon Black Chronic Inflammation Free Radical Free Radicals Inhalation Inhalation Co-exposure Lung Inflammation Mixed Exposures Nanoparticles Ozone Particulates Toxicology Ultrafine Particles

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• ISSN:
  2213-2317
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Michigan ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  46
• NIOSHTIC Number:
  nn:20063449
• Citation:
  Redox Biol 2021 Oct; 46:102092
• Contact Point Address:
  Salik Hussain, Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV, USA
• Email:
  salik.hussain@hsc.wvu.edu
• CAS Registry Number:
  Carbon black (CAS RN 1333-86-4) ; Ozone (CAS RN 10028-15-6)
• Federal Fiscal Year:
  2022
• NORA Priority Area:
  Construction ; Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Redox Biology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1cb985a7dd42b06dbae2391bd72a5e86ed257571d9ea6e22cbbe21c80e113c4e8b88f3cfc766a0ff527d705e8505ea7cfc8536b3217681d302df2e1b63dc87d0
• Download URL:
  https://stacks.cdc.gov/view/cdc/226514/cdc_226514_DS1.pdf
• File Type:
  [PDF - 7.95 MB ]