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Lung-Based, Exosome Inhibition Mediates Systemic Impacts Following Particulate Matter Exposure



Details

  • Personal Author:
  • Description:
    Particulate matter (PM) exposure is a global health issue that impacts both urban and rural communities. Residential communities in the Southwestern United States have expressed concerns regarding the health impacts of fugitive PM from rural, legacy mine-sites. In addition, the recent literature suggests that exosomes may play a role in driving toxicological phenotypes following inhaled exposures. In this study, we assessed exosome-driven mechanisms and systemic health impacts following inhaled dust exposure, using a rodent model. Using an exosome inhibitor, GW4869 (10 µM), we inhibited exosome generation in the lungs of mice via oropharyngeal aspiration. We then exposed mice to previously characterized inhaled particulate matter (PM) from a legacy mine-site and subsequently assessed downstream behavioral, cellular, and molecular biomarkers in lung, serum, and brain tissue. Results indicated that CCL-2 was significantly upregulated in the lung tissue and downregulated in the brain (p < 0.05) following PM exposure. Additional experiments revealed cerebrovascular barrier integrity deficits and increased glial fibrillary acidic protein (GFAP) staining in the mine-PM exposure group, mechanistically dependent on exosome inhibition. An increased stress and anxiety response, based on the open-field test, was noted in the mine-PM exposure group, and subsequently mitigated with GW4869 intervention. Exosome lipidomics revealed 240 and eight significantly altered positive-ion lipids and negative-ion lipids, respectively, across the three treatment groups. Generally, phosphatidylethanolamine (PE) and phosphatidylcholine (PC) lipids were significantly downregulated in the PM group, compared to FA. In conclusion, these data suggest that systemic, toxic impacts of inhaled PM may be mechanistically dependent on lung-derived, circulating exosomes, thereby driving a systemic, proinflammatory phenotype. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    2305-6304
  • Document Type:
    Text
  • Funding:
    Contract
  • Genre:
    Journal Article
  • Place as Subject:
  • CIO:
    National Institute for Occupational Safety and Health (NIOSH)
  • Topic:
    Workplace Safety & Health
  • Location:
    North America
  • Volume:
    10
  • Issue:
    8
  • NIOSHTIC Number:
    nn:20067841
  • Citation:
    Toxics 2022 Aug; 10(8):457
  • Contact Point Address:
    Katherine E. Zychowski, College of Nursing, University of New Mexico-Health Sciences Center, Albuquerque, NM 87131, USA
  • Email:
    kzychowski@salud.unm.edu
  • Federal Fiscal Year:
    2022
  • Performing Organization:
    New Mexico Institute of Mining and Technology
  • Peer Reviewed:
    True
  • Start Date:
    20210901
  • Source Full Name:
    Toxics
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:5c38fc6e0e48d3c4c5261ee7297320e1d38862c868bef60e9b3dccb485e1c11b480157e26730f3a7bc52cd401482b336ef98fb1b3eef516774356116af789563
  • Download URL:
  • File Type:
    Filetype[PDF - 1.91 MB ]
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