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Genetic determinants of sensitivity to beryllium in mice.

Authors
Tarantino-Hutchison-LM; Sorrentino-C; Nadas-A; Zhu-YW; Rubin-EM; Tinkle-SS; Weston-A; Gordon-T
Source
J Immunotoxicol 2009 Jun; 6(2):130-135
NIOSHTIC No.
20035787
Abstract
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.
Keywords
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
Contact
Terry Gordon, PhD, NYU School of Medicine, 57 Old Forge Rd., Tuxedo, NY 10987
CODEN
JIOMAP
CAS No.
7440-41-7
Publication Date
20090601
Document Type
Journal Article
Email Address
terry.gordon@nyumc.org
Fiscal Year
2009
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
1547-691X
NIOSH Division
DRDS; HELD
Priority Area
Manufacturing
Source Name
Journal of Immunotoxicology
State
WV; NY; NC; CA
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