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Herein, we characterized inflammatory cells in the lungs using a murine model of prolonged ozone exposure, with the long-term goal of assessing their role in disease pathogenesis. Mice were exposed to air or ozone (1.5\u2009ppm, 2\u2009h, 2\u00d7\/wk, 6 wk). Bronchoalveolar lavage fluid (BAL) and cells and lung tissue were collected 24\u2009h after the final exposure. Alveolar\/bronchiolar hyperplasia, epithelial degeneration, and mononuclear cell infiltration were observed following ozone exposure; BAL protein, cells, fibrinogen, and SP-A and SP-D were also increased, along with markers of oxidative stress, and impaired pulmonary function. Flow cytometric analysis of infiltrating myeloid cells revealed that after ozone exposure, the majority of these cells were mature infiltrating macrophages. These were comprised mainly of anti-inflammatory\/profibrotic macrophages, with a smaller number of proinflammatory macrophages. Proinflammatory genes (Il1\u03b2, Ccl3, Ccl17, Ccl22, Tnf\u03b1) and NF-\u03baB activity were increased in BAL cells from ozone-exposed mice (&amp;gt;97% macrophages); profibrotic genes (Mmp12, Mmp28, Tgf\u03b2), but not anti-inflammatory genes (Il10, Arg1), were also upregulated. Following ozone exposure, glycolytic activity and oxidative phosphorylation increased in BAL cells, consistent with proinflammatory and profibrotic activation, respectively. These findings are important as they provide a rationale for evaluating the role of inflammatory macrophages in the pathophysiological response to prolonged ozone exposure.<\/jats:p>\n                  <jats:p>Impact statement: These studies are significant as they may lead to the identification of novel therapeutic approaches for reducing inflammatory lung disease caused by long-term exposure to inhaled ozone.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaf173","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T13:06:14Z","timestamp":1765458374000},"source":"Crossref","is-referenced-by-count":1,"title":["Lung injury, oxidative stress, and impaired functioning in a model of prolonged ozone exposure in female mice are associated with macrophage proinflammatory and profibrotic activation and altered bioenergetics"],"prefix":"10.1093","volume":"209","author":[{"given":"Vasanthi R","family":"Sunil","sequence":"first","affiliation":[{"name":"Ernest Mario School of Pharmacy, Rutgers University , Piscataway, NJ 08854,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinal N","family":"Vayas","sequence":"additional","affiliation":[{"name":"Ernest Mario School of Pharmacy, Rutgers University , Piscataway, NJ 08854,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3013-6270","authenticated-orcid":false,"given":"Jared","family":"Radbel","sequence":"additional","affiliation":[{"name":"Robert Wood Johnson Medical School, Rutgers University , New Brunswick, NJ 08901,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ley Cody","family":"Smith","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Connecticut , Storrs, CT 06269,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaclynn A","family":"Meshanni","sequence":"additional","affiliation":[{"name":"Ernest Mario School of Pharmacy, Rutgers University , Piscataway, NJ 08854,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan M","family":"Lee","sequence":"additional","affiliation":[{"name":"Ernest Mario School of Pharmacy, Rutgers University , Piscataway, NJ 08854,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Weinstock","sequence":"additional","affiliation":[{"name":"Ernest Mario School of Pharmacy, Rutgers University , Piscataway, NJ 08854,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Abramova","sequence":"additional","affiliation":[{"name":"Ernest Mario School of Pharmacy, Rutgers University , Piscataway, NJ 08854,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor O","family":"Shmarakov","sequence":"additional","affiliation":[{"name":"School of Environmental and Biological Sciences, Rutgers University , New Brunswick, NJ 08901,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J","family":"Gow","sequence":"additional","affiliation":[{"name":"Ernest Mario School of Pharmacy, Rutgers University , Piscataway, NJ 08854,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D","family":"Laskin","sequence":"additional","affiliation":[{"name":"School of Public Health, Rutgers University , Piscataway, NJ 08854,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra L","family":"Laskin","sequence":"additional","affiliation":[{"name":"Ernest Mario School of Pharmacy, Rutgers University , Piscataway, NJ 08854,","place":["United 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