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
Year: 2025
Type: article
Abstract: Prolonged exposure to ozone causes lung injury and persistent inflammation, pathologies associated with emphysema and asthma. 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 ppm, 2 h, 2×/wk, 6 wk). Bronchoalveolar lavage fluid (BAL) and cells and lung tissue were collected 24 h 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 (Il1β, Ccl3, Ccl17, Ccl22, Tnfα) and NF-κB activity were increased in BAL cells from ozone-exposed mice (>97% macrophages); profibrotic genes (Mmp12, Mmp28, Tgfβ), 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. 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.
Source: Toxicological Sciences
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: green
Awards: Beckman Coulter MoFlo Astrios EQ Cell Sorter, Vitamin A metabolism in the adult lung, Role of Macrophage Efferocytosis in Ozone-Induced ARDS, G9000021994, G9000073616, G9000112377, G9000113935, G9000307364, Harnessing Inflammatory Macrophages to Thwart Lung Disease Caused by Chronic Ozone Exposure, Training in Environmental Toxicology, Rutgers Center for Environmental Exposure and Disease (CEED), Estrogen receptor signaling, inflammation and ozone toxicity, Activated Macrophages and Ozone Toxicity
OpenAlex ID: W4417354709