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Enhanced cytotoxic potential of alveolar macrophages from cigarette smokers
W B Davis1, E R Pacht, M Spatafora
1Department of Internal Medicine, Ohio State University, Columbus.
Abstract:
Cigarette smoking increases the numbers and oxidative metabolism of alveolar macrophages. Increased production of superoxide (O2-) and H2O2 by alveolar macrophages may contribute to the pathogenesis of cigarette-induced lung diseases. The cytotoxicity mediated by alveolar macrophages from smokers (n = 11) and nonsmokers (n = 13) was compared in an in vitro assay in which the target cells were chromium 51-labeled lung explants. The spontaneous cellular cytotoxicity mediated by smoker macrophages was significantly greater than that of nonsmoker macrophages (cytotoxic index 20.3% +/- 1.9% compared with 5.5% +/- 0.9%, P less than 0.001). Phorbol myristate acetate significantly increased the cytotoxic index of nonsmoker macrophages but did not cause further increases in smoker macrophage killing. The antioxidants superoxide dismutase and catalase produced partial inhibition of smoker macrophage cytotoxicity, suggesting that target cell killing was mediated in part by oxidant mechanisms. Supplementation of smokers' diets with high-dose oral vitamin E failed to decrease smoker alveolar macrophage cytotoxicity. These findings demonstrate that smoker alveolar macrophages possess enhanced cytotoxic potential for normal lung parenchymal cells.
Insights
Smoker alveolar macrophages exhibit heightened cytotoxicity against lung cells, potentially contributing to smoking-related lung diseases. Antioxidants partially inhibited this effect, but vitamin E supplementation did not reduce it.
Area of Science:
- Pulmonary Medicine
- Immunology
- Toxicology
Background:
- Cigarette smoking elevates alveolar macrophage numbers and oxidative metabolism.
- Increased reactive oxygen species production by macrophages may drive cigarette-induced lung diseases.
Purpose of the Study:
- To compare the cytotoxic potential of alveolar macrophages from smokers versus nonsmokers.
- To investigate the role of oxidant mechanisms in macrophage-mediated cytotoxicity.
- To assess the effect of vitamin E on smoker macrophage cytotoxicity.
Main Methods:
- In vitro assay comparing cytotoxicity of alveolar macrophages from smokers (n=11) and nonsmokers (n=13).
- Target cells were chromium 51-labeled lung explants.
- Assessment of cytotoxicity with and without phorbol myristate acetate and antioxidants (superoxide dismutase, catalase).
Main Results:
- Spontaneous cytotoxicity was significantly higher in smoker macrophages (20.3% +/- 1.9%) than nonsmoker macrophages (5.5% +/- 0.9%).
- Phorbol myristate acetate enhanced nonsmoker macrophage cytotoxicity but not smoker macrophage cytotoxicity.
- Antioxidants partially inhibited smoker macrophage cytotoxicity, indicating oxidant involvement.
- High-dose vitamin E supplementation did not reduce smoker macrophage cytotoxicity.
Conclusions:
- Alveolar macrophages from smokers demonstrate enhanced cytotoxic activity against normal lung parenchymal cells.
- Oxidative mechanisms contribute to the cytotoxic potential of smoker alveolar macrophages.
- Vitamin E is ineffective in mitigating this enhanced cytotoxicity.