Article

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: 5.27). 05/2005; 38(7):928-37. DOI: 10.1016/j.freeradbiomed.2004.12.014
Source: PubMed

ABSTRACT 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.

0 Bookmarks
 · 
77 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the effects of short-term exposure of beryllium on the human immune system, the proportion of T-lymphocytes such as CD3+, CD4+, CD8+, CD95, and NK cells, andthe proportion of B cells and TNFα level in peripheral blood and immunoglobulins in the serum of 43 exposed workers and 34 healthy control subjects were studied. External exposure to beryllium was measured by atomic absorption spectrometer as recommended by the NIOSH analytical method 7300. T lymphocyte subpopulation analysis was carried out with flow cytometer. The working duration of exposed workers was less than 3 months and the mean ambient beryllium level was 3.4 μg/m(3), 112.3 μg/m(3), and 2.3 μg/m(3) in molding (furnace), deforming (grinding), and sorting processes, respectively (cited from Kim et al., 2008). However, ambient beryllium level after process change was non-detectable (< 0.1 μg/m(3)). The number of T lymphocytes and the amount of immunoglobulins in the beryllium-exposed workers and control subjects were not significantly different, except for the total number of lymphocytes and CD95 (APO1/FAS). The total number of lymphocytes was higher in the beryllium-exposed individuals than in the healthy control subjects. Multiple logistic regression analysis showed lymphocytes to be affected by beryllium exposure (odd ratio = 7.293; p < 0.001). These results show that short-term exposure to beryllium does not induce immune dysfunction but is probably associated with lymphocytes proliferation.
    Toxicological research. 06/2013; 29(2):115-120.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The exposure-response patterns with beryllium sensitization (BeS), chronic beryllium disease (CBD) and lung cancer are influenced by a number of biological and physicochemical factors. Recent studies have suggested dermal exposure as a pathway for BeS. In light of the current non-health-based DOE Beryllium Rule surface criteria, the feasibility of deriving a human health-based surface dust cleanup criteria (SDCC) for beryllium was assessed based on toxicology and health risk factors via all potential routes of exposure. Beryllium-specific and general exposure factors were evaluated, including (1) beryllium physicochemical characteristics, bioavailability and influence on disease prevalence, and (2) chemical dissipation, resuspension and transfer. SDCC for non-cancer (SDCC) and cancer (SDCC) endpoints were derived from a combination of modern methods applied for occupational, residential and building reentry surface dust criteria. The most conservative SDCC estimates were derived for dermal exposure (5-379 μg/100 cm for 0.1-1% damaged skin and 17-3337 μg/100 cm for intact skin), whereas the SDCC for inhalation exposure ranged from 51 to 485 μg/100 cm. Considering this analysis, the lowest DOE surface criterion of 0.2 μg/100 cm is conservative for minimizing exposure and potential risks associated with beryllium-contaminated surfaces released for non-beryllium industrial or public sector use. Although methodological challenges exist with sampling and analysis procedures, data variability and interpretation of surface dust information in relation to anthropogenic and natural background concentrations, this evaluation should provide useful guidance with regard to cleanup of manufacturing equipment or remediation of property for transfer to the general public or non-beryllium industrial facilities.
    Critical Reviews in Toxicology 03/2013; 43(3):220-43. · 6.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This review describes the health effects of beryllium exposure in the workplace and the environment. To collate information on the consequences of occupational and environmental exposure to beryllium on physiological function and well being. The criteria used in the current review for selecting articles were adopted from proposed criteria in The International Classification of Functioning, Disability, and Health. Articles were classified based on acute and chronic exposure and toxicity of beryllium. The proportions of utilized and nonutilized articles were tabulated. Years 2001-10 gave the greatest match (45.9%) for methodological parameters, followed by 27.71% for 1991-2000. Years 1971-80 and 1981-90 were not significantly different in the information published and available whereas years 1951-1960 showed a lack of suitable articles. Some articles were published in sources unobtainable through requests at the British Library, and some had no impact factor and were excluded. Beryllium has some useful but undoubtedly harmful effects on health and well-being. Measures need to be taken to prevent hazardous exposure to this element, making its biological monitoring in the workplace essential.
    Indian journal of occupational and environmental medicine 08/2009; 13(2):65-76.