title: Beryllium uptake and related biological effects studied in THP-1 differentiated macrophages.
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 hypersensitivity immune response to a beryllium-containing antigen. In the present work, human monocyte cell 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 BeSO(4), 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.
authors.affiliation: Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Key Laboratory of Analytical Science, Xiamen University, Xiamen 361005, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Wei
authors.initials: W
authors.lastname: Hang
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Yan
mesh_terms: D001608:Beryllium / Q000493:pharmacokinetics / Q000494:pharmacology*; D015153:Blotting, Western; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007951:Leukemia, Myeloid; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010587:Phagocytosis / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D001608:Beryllium