{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:00:00Z","timestamp":1792000800445,"version":"4.4.0"},"reference-count":49,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T00:00:00Z","timestamp":1659830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institutes of Health (NIH\/NIEHS)","doi-asserted-by":"publisher","award":["K99\/R00 ES029104"],"award-info":[{"award-number":["K99\/R00 ES029104"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institutes of Health (NIH\/NIEHS)","doi-asserted-by":"publisher","award":["R21 ES032432"],"award-info":[{"award-number":["R21 ES032432"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institutes of Health (NIH\/NIEHS)","doi-asserted-by":"publisher","award":["P42 ES025589"],"award-info":[{"award-number":["P42 ES025589"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institutes of Health (NIH\/NIEHS)","doi-asserted-by":"publisher","award":["75D30121C12182"],"award-info":[{"award-number":["75D30121C12182"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centers for Disease Control and Prevention (CDC\/NIOSH)","award":["K99\/R00 ES029104"],"award-info":[{"award-number":["K99\/R00 ES029104"]}]},{"name":"Centers for Disease Control and Prevention (CDC\/NIOSH)","award":["R21 ES032432"],"award-info":[{"award-number":["R21 ES032432"]}]},{"name":"Centers for Disease Control and Prevention (CDC\/NIOSH)","award":["P42 ES025589"],"award-info":[{"award-number":["P42 ES025589"]}]},{"name":"Centers for Disease Control and Prevention (CDC\/NIOSH)","award":["75D30121C12182"],"award-info":[{"award-number":["75D30121C12182"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>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 \u03bcM), 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 &lt; 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.<\/jats:p>","DOI":"10.3390\/toxics10080457","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T09:47:06Z","timestamp":1660124826000},"page":"457","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Lung-Based, Exosome Inhibition Mediates Systemic Impacts Following Particulate Matter Exposure"],"prefix":"10.3390","volume":"10","author":[{"given":"Keegan","family":"Lopez","sequence":"first","affiliation":[{"name":"Department of Biology, College of Arts and Sciences, New Mexico Highlands University, Las Vegas, NM 88901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Camacho","sequence":"additional","affiliation":[{"name":"College of Nursing, University of New Mexico-Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quiteria","family":"Jacquez","sequence":"additional","affiliation":[{"name":"College of Nursing, University of New Mexico-Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Kay","family":"Amistadi","sequence":"additional","affiliation":[{"name":"Arizona Laboratory for Emerging Contaminants, University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Medina","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Arts and Sciences, New Mexico Highlands University, Las Vegas, NM 88901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5751-2897","authenticated-orcid":false,"given":"Katherine","family":"Zychowski","sequence":"additional","affiliation":[{"name":"College of Nursing, University of New Mexico-Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1080\/15287394.2020.1830210","article-title":"Assessment of particulate matter toxicity and physicochemistry at the Claim 28 uranium mine site in Blue Gap, AZ","volume":"84","author":"Begay","year":"2021","journal-title":"J. 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