Beryllium-stimulated reactive oxygen species and macrophage apoptosis

Department of Medicine, Robert H. Hollis Laboratory of Environmental and Occupational Health Sciences, National Jewish Medical and Research Center, Denver, 1400 Jackson Street, CO 80206, USA.
Free Radical Biology and Medicine (Impact Factor: 5.74). 05/2005; 38(7):928-37. DOI: 10.1016/j.freeradbiomed.2004.12.014
Source: PubMed


Beryllium (Be), the etiologic agent of chronic beryllium disease, is a toxic metal that induces apoptosis in human alveolar macrophages. We tested the hypothesis that Be stimulates the formation of reactive oxygen species (ROS) which plays a role in Be-induced macrophage apoptosis. Mouse macrophages were exposed to 100 microM BeSO4 in the absence and presence of the catalytic antioxidant MnTBAP (100 microM). Apoptosis was measured as the percentage of TUNEL+ and caspase-8+ cells. ROS production was measured by flow cytometry using the fluorescence probes, dihydroethidine (DHE) and dichlorofluorescein diacetate (DCFH-DA). Be-exposed macrophages had increased TUNEL+ cells (15+/-1% versus controls 1+/-0.2%, P<0.05) and increased caspase-8+ cells (18.7+/-2% versus controls 1.8+/-0.4%, P<0.05). Be-induced caspase-8 activation, and a 4-fold increase in ROS formation, was ameliorated by exposure to MnTBAP. Hydrogen peroxide (30 microM) exposure potentiated Be-induced caspase-8 activation, and was also attenuated by MnTBAP. Our data are the first to demonstrate that Be stimulates macrophage ROS formation which plays an important role in Be-induced macrophage apoptosis.

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    Scientific Reports 07/2013; 3:2233. DOI:10.1038/srep02233 · 5.58 Impact Factor
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    • "Therefore, it is impossible to check directly whetherthere is a possibility that short-term exposure can cause apoptosis. However, the increase of lymphocyte is associated with an increase of inflammatory response, and it may be explained as a result of the inflammatory response and the accompanying oxidative stress by exposure to beryllium (26). Eventually, inflammatory response associated with an increase in macrophage apoptosis, the probability is deemed sufficient. "
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    • "Be is believed to stimulate the formation of ROS, leading to Beinduced macrophage apoptosis [99]. While the molecular mechanisms of Be-induced toxicity have yet to be elucidated, macrophage apoptosis is thought to contribute to the metalinduced CBD [99] [100]. Be is also suspected to induce oxidative stress through the depletion of endogenous thiol antioxidants and the subsequent increase in ROS generation [101]. "
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