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Acute cigarette smoke exposure induces apoptosis of alveolar macrophages
K Aoshiba1, J Tamaoki, A Nagai
1First Department of Medicine, Tokyo Women's Medical University, Shinjuku-ku, Tokyo 162-8666, Japan. kaoshiba@chi.twmu.ac.jp
Abstract:
Alveolar macrophages (AMs) may play a critical role in cigarette smoke (CS)-related pulmonary diseases. This study was designed to determine whether CS induces apoptosis of AMs. In in vitro studies, mouse, rat, and human AMs and human blood monocyte-derived macrophages cultured with aqueous whole CS extracts underwent apoptosis that was detected by light and electron microscopy and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling. The gas phase of CSE did not cause apoptosis. The CS-induced apoptosis was associated with increased oxidative stress, Bax protein accumulation, mitochondrial dysfunction, and mitochondrial cytochrome c release but was independent of p53, Fas, and caspase activation. This apoptosis was inhibited by antioxidants such as glutathione, ascorbic acid, and alpha-tocopherol. In in vivo studies where rats were exposed to the smoke from 10 cigarettes over 5 h in an exposure chamber, approximately 3% of AMs obtained by bronchoalveolar lavage after 24 h showed apoptosis. These results suggest that acute CS exposure is capable of inducing apoptosis of AMs.
Insights
Cigarette smoke (CS) triggers apoptosis, or programmed cell death, in alveolar macrophages (AMs). Antioxidants can prevent this effect, suggesting a role for oxidative stress in CS-induced lung injury.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Toxicology
Background:
- Alveolar macrophages (AMs) are crucial in lung health and disease.
- Cigarette smoke (CS) is a major risk factor for pulmonary diseases.
Purpose of the Study:
- To investigate if CS exposure induces apoptosis in AMs.
- To elucidate the mechanisms underlying CS-induced AM apoptosis.
Main Methods:
- In vitro studies using mouse, rat, and human AMs exposed to CS extracts.
- In vivo rat model exposed to CS.
- Apoptosis detection via microscopy and TUNEL assay.
- Analysis of oxidative stress, mitochondrial function, and key proteins (Bax, p53, caspases).
Main Results:
- Aqueous CS extracts induced apoptosis in all tested AMs, but the gas phase did not.
- CS-induced apoptosis involved oxidative stress, Bax accumulation, and mitochondrial dysfunction, independent of p53, Fas, and caspase activation.
- Antioxidants (glutathione, ascorbic acid, alpha-tocopherol) inhibited CS-induced apoptosis.
- In vivo CS exposure resulted in approximately 3% AM apoptosis.
Conclusions:
- Acute CS exposure induces AM apoptosis.
- Oxidative stress and mitochondrial pathways are key mediators of CS-induced AM apoptosis.
- Targeting oxidative stress may offer therapeutic potential for CS-related lung diseases.