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Genetic determinants of sensitivity to beryllium in mice.
Tarantino-Hutchison-LM; Sorrentino-C; Nadas-A; Zhu-YW; Rubin-EM; Tinkle-SS; Weston-A; Gordon-T
J Immunotoxicol 2009 Jun; 6(2):130-135
Chronic beryllium disease (CBD), an irreversible, debilitating granulomatous lung disease is caused by exposure to beryllium. This occupational hazard occurs in primary production and machining of Be-metal, BeO, beryllium containing alloys, and other beryllium products. CBD begins as an MHC Class II-restricted, T(H)1 hypersensitivity, and the Human Leukocyte Antigen, HLA-DPB1E(69), is associated with risk of developing CBD. Because inbred strains of mice have not provided good models of CBD to date, three strains of HLA-DPB1 transgenic mice in an FVB/N background were developed; each contains a single allele of HLA-DPB1 that confers a different magnitude of risk for chronic beryllium disease: HLA-DPB1*0401 (OR approximate to 0.2), HLA-DPB1*0201 (OR approximate to 3), and HLA-DPB1*1701 (OR approximate to 46). The mouse ear swelling test ( MEST) was employed to determine if these different alleles would support a hypersensitivity response to beryllium. Mice were first sensitized on the back and subsequently challenged on the ear. In separate experiments, mice were placed into one of three groups (sensitization/challenge): C/C, C/Be, and Be/Be. In the HLA-DPB1*1701 mice, the strain with the highest risk transgene, the Be/Be group was the only group that displayed significant maximum increased ear thickness of 19.6% +/- 3.0% over the baseline measurement (p < 0.05). No significant changes were observed in the other transgenic strains for any treatment condition. In addition, inter-strain differences in response to beryllium in seven inbred strains were investigated through use of the MEST, these included: FVB/N, AKR, Balb/c, C3H/HeJ, C57/BL6, DBA/2, and SJL/J. The FVB/N strain was least responsive, while the SJL/J and C57/BL6 strains were the highest responders. Our results suggest that the HLA-DPB1*1701 transgene product is an important risk factor for induction of the beryllium-sensitive phenotype. This model should be a useful tool for investigating beryllium sensitization.
Antigens; Beryllium-disease; Biochemical-analysis; Biochemistry; Biohazards; Biological-effects; Biological-factors; Biological-function; Biological-systems; Chemical-hypersensitivity; Chemical-manufacturing-industry; Chemical-properties; Exposure-assessment; Exposure-levels; Exposure-methods; Health-hazards; Inhalation-studies; Laboratory-animals; Laboratory-testing; Lung-disease; Lung-disorders; Lung-irritants; Metal-dusts; Metal-fumes; Metal-poisoning; Metal-workers; Metalworking; Metalworking-industry; Occupational-diseases; Occupational-exposure; Occupational-hazards; Occupational-respiratory-disease; Pulmonary-disorders; Pulmonary-system; Pulmonary-system-disorders; Statistical-analysis; Work-environment; Worker-health; Work-practices; Author Keywords: Beryllium; chronic beryllium disease; mouse model
Terry Gordon, PhD, NYU School of Medicine, 57 Old Forge Rd., Tuxedo, NY 10987
Issue of Publication
Journal of Immunotoxicology
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Page last reviewed: May 5, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division