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Beryllium-stimulated apoptosis in macrophage cell lines
R T Sawyer1, V A Fadok, L A Kittle
1Division of Environmental and Occupational Health Sciences, Department of Medicine, D309 Neustadt, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA. sawyerr@njc.org
Toxicology
|September 1, 2000
Summary
Beryllium exposure causes macrophage cell death (apoptosis) in chronic beryllium disease (CBD). This caspase-dependent apoptosis is not solely driven by TNF-alpha, suggesting a complex inflammatory cycle in the lungs.
Area of Science:
- Immunology
- Cell Biology
- Toxicology
Background:
- Chronic beryllium disease (CBD) involves inflammation in the lungs triggered by beryllium exposure.
- Tumor necrosis factor-alpha (TNF-alpha) is a key cytokine implicated in CBD pathogenesis.
- The role of beryllium-stimulated TNF-alpha in macrophage apoptosis within CBD is not fully understood.
Purpose of the Study:
- To investigate whether beryllium (Be)-stimulated TNF-alpha induces apoptosis in mouse and human macrophage cell lines.
- To determine if beryllium sulfate (BeSO4) induces apoptosis in macrophage cell lines.
- To elucidate the role of caspases in beryllium-induced apoptosis.
Main Methods:
- Utilized mouse (H36.12j, P388D.1) and human (DEOHS-1) macrophage cell lines with varying TNF-alpha production.
- Stimulated cell lines with beryllium sulfate (BeSO4) and observed apoptosis via propidium iodide staining of fragmented nuclei.
- Assessed apoptosis using a general caspase inhibitor (BD-fmk) to determine caspase dependency.
Main Results:
- Beryllium sulfate (BeSO4) induced dose-responsive apoptosis in all tested macrophage cell lines.
- Apoptosis was maximal after 24 hours of exposure to 100 microM BeSO4.
- BeSO4-stimulated apoptosis was inhibited by a caspase inhibitor, indicating a caspase-dependent mechanism, independent of TNF-alpha levels.
Conclusions:
- Beryllium exposure directly induces caspase-dependent apoptosis in macrophages.
- Beryllium-stimulated apoptosis is not solely dependent on TNF-alpha levels.
- Released beryllium antigen from apoptotic macrophages may perpetuate lung inflammation and granuloma formation in CBD.