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The aim of this study was to develop a murine model of ALI to mechanistically explore the impact of ozone exposure on ARDS development. Mice were exposed to ozone (0.8\u2009ppm, 3\u2009h) or air control followed 24\u2009h later by intravenous administration of 3\u2009mg\/kg lipopolysaccharide (LPS) or PBS. Exposure of mice to ozone + LPS caused alveolar hyperplasia; increased BAL levels of albumin, IgM, phospholipids, and proinflammatory mediators including surfactant protein D and soluble receptor for advanced glycation end products were also detected in BAL, along with markers of oxidative and nitrosative stress. Administration of ozone + LPS resulted in an increase in neutrophils and anti-inflammatory macrophages in the lung, with no effects on proinflammatory macrophages. Conversely, the numbers of resident alveolar macrophages decreased after ozone + LPS; however, expression of Nos2, Arg1, Cxcl1, Cxcl2, Ccl2 by these cells increased, indicating that they are activated. These findings demonstrate that ozone sensitizes the lung to respond to endotoxin, resulting in ALI, oxidative stress, and exacerbated pulmonary inflammation, and provide support for the epidemiologic association between ozone exposure and ARDS incidence.<\/jats:p>","DOI":"10.1093\/toxsci\/kfae062","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T20:13:31Z","timestamp":1715804011000},"page":"299-311","source":"Crossref","is-referenced-by-count":12,"title":["Effects of ozone exposure on lung injury, inflammation, and oxidative stress in a murine model of nonpneumonic endotoxemia"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3013-6270","authenticated-orcid":false,"given":"Jared","family":"Radbel","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Pulmonary and Critical Care Medicine, Rutgers Robert Wood Johnson Medical School , New Brunswick, New Jersey 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaclynn A","family":"Meshanni","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University , Piscataway, New Jersey 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinal N","family":"Vayas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University , Piscataway, New Jersey 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oahn","family":"Le-Hoang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary and Critical Care Medicine, Rutgers Robert Wood Johnson Medical School , New Brunswick, New Jersey 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Abramova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University , Piscataway, New Jersey 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peihong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University , Piscataway, New Jersey 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie B","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University , Piscataway, New Jersey 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D","family":"Laskin","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health and Justice, School of Public Health, Rutgers University , Piscataway, New Jersey 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J","family":"Gow","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University , Piscataway, New Jersey 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra L","family":"Laskin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University , Piscataway, New Jersey 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"2024072915000547200_kfae062-B2","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1165\/rcmb.2003-0091OC","article-title":"Surfactant protein-D, a mediator of innate lung immunity, alters the products of nitric oxide metabolism","volume":"30","author":"Atochina","year":"2004","journal-title":"Am. 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