Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-7-10
pubmed:abstractText
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 approximately 0.2), HLA-DPB1*0201 (OR approximately 3), and HLA-DPB1*1701 (OR approximately 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1547-6901
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
130-5
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:19589099-Alleles, pubmed-meshheading:19589099-Animals, pubmed-meshheading:19589099-Berylliosis, pubmed-meshheading:19589099-Beryllium, pubmed-meshheading:19589099-Disease Models, Animal, pubmed-meshheading:19589099-Genetic Predisposition to Disease, pubmed-meshheading:19589099-HLA-DP Antigens, pubmed-meshheading:19589099-HLA-DP beta-Chains, pubmed-meshheading:19589099-Humans, pubmed-meshheading:19589099-Hypersensitivity, Delayed, pubmed-meshheading:19589099-Mice, pubmed-meshheading:19589099-Mice, Inbred Strains, pubmed-meshheading:19589099-Mice, Transgenic, pubmed-meshheading:19589099-Polymorphism, Genetic, pubmed-meshheading:19589099-Risk Factors, pubmed-meshheading:19589099-Skin Tests, pubmed-meshheading:19589099-Species Specificity, pubmed-meshheading:19589099-Th1 Cells
pubmed:year
2009
pubmed:articleTitle
Genetic determinants of sensitivity to beryllium in mice.
pubmed:affiliation
Department of Environmental Medicine, NYU School of Medicine, Tuxedo, New York 10987, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural