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Issue 6, 2009
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Beryllium uptake and related biological effects studied in THP-1 differentiated macrophages

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Abstract

Investigation of cellular uptake of metal compounds is important in understanding metal-related toxicity and diseases. Inhalation of beryllium aerosols can cause chronic beryllium disease, a progressive, granulomatous fibrosis of the lung. Studies in laboratory animals and cultured animal cells indicate that alveolar macrophages take up beryllium compounds and participate in a hypersensitivityimmune response to a beryllium-containing antigen. In the present work, human monocytecell line THP-1 was induced with phorbol myristate acetate to differentiate into a macrophage. This cell with characteristics of human alveolar macrophages was employed to study cellular beryllium uptake and related biological effects. Morphological changes, phagocytosis of fluorescent latex beads, and cell surface CD14 expression were used to verify the successful differentiation of THP-1 monocytes into macrophages. An improved mass spectrometry method for quantitative analysis of intracellular beryllium as opposed to the traditional radioisotopic approach was developed using ICP-MS. The influence of the solubility of beryllium compounds, exposure duration, and beryllium concentration on the incorporation of beryllium was studied. Our data indicated that the uptake of particulate BeO was much more significant than that of soluble BeSO4, suggesting the major cellular uptake pathway is phagocytosis. Nevertheless, subsequent DAPI nuclear staining and PARP cleavage study indicated that beryllium uptake had a negligible effect on the apoptosis of THP-1 macrophages compared to the unstimulated macrophage control. Meanwhile, no substantial variation of tumour necrosis factor-alpha production was observed for THP-1 macrophages upon beryllium exposure. These data imply alveolar macrophages could have some level of tolerance to beryllium and this may explain why most Be-exposed individuals remain healthy throughout life.

Graphical abstract: Beryllium uptake and related biological effects studied in THP-1 differentiated macrophages

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Publication details

The article was received on 08 Jul 2009, accepted on 25 Aug 2009 and first published on 14 Sep 2009


Article type: Paper
DOI: 10.1039/B913265A
Metallomics, 2009,1, 471-478

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    Beryllium uptake and related biological effects studied in THP-1 differentiated macrophages

    J. Ding, L. Lin, W. Hang and X. Yan, Metallomics, 2009, 1, 471
    DOI: 10.1039/B913265A

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