Beryllium-induced sensitization and granulomatous lung disease in murine models.
Tarantino-LM; Hubbs-AF; Hoover-MD; Delano-DL; Wiltshire-T; Gordon-T
Toxicologist 2008 Mar; 102(1):223
Beryllium (Be) exposure is an occupational hazard that can cause chronic beryllium disease (CBD), an irreversible, debilitating granulomatous lung disease, in as many as 3-5% of exposed workers. CBD may be viewed as a biphasic disease: first with peripheral sensitization occurring, and then, in some, progression to pulmonary granuloma formation. To look at both aspects of the disease process, we performed a mouse ear-swelling test (MEST) to correlate with the sensitization process and a 5-month oropharyngeal aspiration study to examine pulmonary granuloma development in mice. Previously, a MEST was utilized to see if different inbred mouse strains would exhibit varying hypersensitivity responses to Be. In the present study, 21 inbred mouse strains were tested for sensitization to Be and distinct strain differences were observed with the mouse ear-swelling test with the SJL/J strain being the most sensitive while the FVB/N strain was resistant. The data were analyzed using an in silico approach to uncover genes associated with sensitization to beryllium and Vav3, involved in the activation of T cell receptors, became a likely candidate. In the current aspiration study, 26 inbred strains were aspirated with either 20ug of beryllium metal particles or water monthly. Clear strain differences in beryllium-induced lymphogranulomatus nodules were observed. In silico analysis was performed on the data and candidate genes implicated in granuloma formation were uncovered and compared to the results of the MEST study. Elucidating genes responsible for the hypersensitive phenotype and granuloma formation in mice may prove useful in learning more about the mechanisms involved in the progression of CBD.
Fumes; Lung; Lung-cells; Lung-disease; Lung-disorders; Lung-irritants; Inhalation-studies; Breathing-zone; Pulmonary-disorders; Pulmonary-system-disorders; Laboratory-animals; Genetic-factors
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington