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Updated: Jun 15, 2026
In Vivo Assessment of Alveolar Macrophage Efferocytosis Following Ozone Exposure
Published on: October 22, 2019
Macrophages that survive hyperoxia exposure have higher superoxide dismutase activities in their mitochondria
Kenichi Kokubo1, Saki Soeda, Toshihiro Shinbo
1Department of Medical Engineering and Technology, School of Allied Health Sciences, Kitasato University, Kanagawa 228-8555, Japan. kokubo@kitasato-u.ac.jp
Abstract:
Prolonged exposure to hyperoxia, which is routinely used in patients with severe respiratory failure, leads to the generation of excessive reactive oxygen species, resulting in lung injury. In the present study, we focused on macrophages and their survival, superoxide dismutase (SOD) activity in mitochondria (Mn-SOD activity), and mitochondrial DNA (mtDNA) mutation after exposure to hyperoxia. Macrophages were cultured under two different conditions: normoxia and intermittent hyperoxia. The number of cells exposed to intermittent hyperoxia for 3 weeks significantly decreased, compared with the number of cells exposed to normoxia. The Mn-SOD activity of the cells that survived intermittent hyperoxia exposure was significantly higher than that of the cells exposed to normoxia. Direct sequencing and a PCR-RFLP assay did not provide any evidence of mutation in the cells that survived intermittent hyperoxia exposure. In conclusion, an increase in the antioxidative activity of mitochondria is important for the survival of macrophages exposed to hyperoxia, and the increased activity level possibly enhances protective effects against mtDNA mutations in surviving cells.
Insights
Prolonged exposure to high oxygen levels (hyperoxia) can harm lung cells. This study found that increased mitochondrial antioxidant activity helps macrophages survive hyperoxia and may protect mitochondrial DNA from damage.
Area of Science:
- Cell Biology
- Biochemistry
- Respiratory Medicine
Background:
- Prolonged exposure to hyperoxia, common in severe respiratory failure treatment, generates reactive oxygen species, leading to lung injury.
- Macrophages play a crucial role in lung immunity and are susceptible to oxidative stress.
Purpose of the Study:
- To investigate the effects of intermittent hyperoxia on macrophage survival.
- To examine mitochondrial superoxide dismutase (Mn-SOD) activity and mitochondrial DNA (mtDNA) mutation in macrophages exposed to hyperoxia.
Main Methods:
- Macrophages were cultured under normoxia and intermittent hyperoxia for 3 weeks.
- Cell counts, Mn-SOD activity assays, and molecular analyses (direct sequencing, PCR-RFLP) were performed.
Main Results:
- A significant decrease in macrophage number was observed under intermittent hyperoxia compared to normoxia.
- Surviving macrophages exhibited significantly higher Mn-SOD activity.
- No evidence of mtDNA mutation was found in surviving macrophages.
Conclusions:
- Increased mitochondrial antioxidative activity is vital for macrophage survival during hyperoxia.
- Enhanced Mn-SOD activity may confer protective effects against mtDNA mutations in surviving macrophages.
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