US EPA

3544762 

Journal Article 

Asbestos-Induced Autoimmunity In C57BL/6 Mice 

Pfau, JC; Sentissi, J; Thompson, R; Mackenzie, C 

2005 

1 

Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929 

84 

1-S 

186 

English 

Environmental impacts on autoimmunity have significant public health implications. Epidemiological studies have shown associations between exposure to airborne silicates, such as crystalline silica or asbestos, and autoimmunity, but the etiology remains unclear. A mouse model is needed to explore mechanisms of asbestos-associated autoimmunity. In order to determine whether asbestos could lead to autoimmune responses in mice, female C57Bl/6 mice were instilled intratracheally with tremolite asbestos, wollastonite, or saline. Serum samples were collected via saphenous vein bleeds and urine was checked for protein bi-weekly for 7 months, at which time tissue and serum samples were taken following sacrifice. Tremolite, but neither wollastonite nor saline, led to cellular infiltrations and fibrosis, as measured by histology and Lucifer yellow staining. By 26 weeks, the tremolite- instilled animals had a significantly higher frequency of positive anti-nuclear antibody (ANA) tests compared to wollastonite and saline groups. Of those positive ANAs, most showed homogeneous or combined homogeneous/speckled patterns on HEp-2 cells, and tested positive for antibodies to dsDNA by ELISA. Although no glomerulonephritis was apparent according to proteinurea tests, immune complex deposition was demonstrated in the kidneys of tremolite-instilled mice. There was an overall decrease in the mean IgG serum concentration in tremolite-instilled mice. Flow cytometry demonstrated a significant decrease in the percentage of CD25 T suppressor cells and an increase in the percentage of B1a B cells in the cervical lymph nodes of the tremolite-instilled mice, consistent with changes seen in autoimmune-prone mice. These data demonstrate that tremolite asbestos led to lung fibrosis as well as immunologic changes consistent with the development of autoimmunity. This study demonstrates a murine model of asbestos-induced autoimmunity, which can be used to elucidate the mechanisms leading to these responses. 

Mice; Animals; Mice, Inbred C57BL; Asbestos/TOXICITY; Autoimmune Diseases/CHEMICALLY INDUCED; Enzyme-Linked Immunosorbent Assay; Immunoglobulin G/BLOOD; Flow Cytometry; Models, Animal; 1332-21-4; NO CAS RN