Effect of Perfluorooctanesulfonic acid (PFOS) on immune cell development and function in mice

Abstract

Perfluorinated compounds, such as Perfluoroctane sulfonic acid (PFOS) are compounds containing carbon chains where hydrogens have been replaced with fluorines, and belong to a larger family known as Per-and polyfluoroalkyl substances (PFAS). The strength of the carbonfluorine bond makes perfluorinated compounds extremely resistant to environmental degradation.Due to the persistent nature of PFOS, research has been directed to elucidating possible health effects of PFOS on humans and laboratory animals. Here we have explored the effects of PFOS exposure on immune development and function in mice. We exposed adult wild-type mice to 3 and 1.5 μg/kg/day of PFOS for 2 and 4 weeks, respectively, and examined the effects of PFOS exposure on populations of T cells, B cells, and granulocytes. These doses of PFOS resulted in serum levels of approximately 100 ng/ml with no weight loss during exposure. We find that PFOS does not affect T-cell development during this time. However, while PFOS exposure reduced immune cell populations in some organs, it also led to an increase in the numbers of cells in others, suggesting possible relocalization of cells. We also examined the effect of PFOS on the response to influenza virus infection. We find that exposure to PFOS at 1.5 μg/kg/day of PFOS for 4 weeks does not affect weight loss or survival, nor is viral clearance affected. Analysis of antibody and T cell specific antiviral responses indicate that at this concentration, PFOS does not suppress the immune cell development or antigen specific immune response. corticosteroids (a known confounder for immune response 13 ), that accompanies these high dose treatments cannot be excluded 12 .Here we have evaluated the potential immunotoxicity of exposure to PFOS in wild-type C57Bl/6 mice after repeated oral treatments for either 2 weeks or 4 weeks, using doses of PFOS that did not lead to weight loss in the animals. We examined the development of immune cells, including T cell development in the thymus, as well as B cell and granulocyte development in the bone marrow and spleen. We also evaluated the effect of PFOS exposure on the immune response to influenza virus infection. Materials and Methods MaterialAll chemicals used in this study were reagent-grade. Potassium perfluorooctanesulfonate (K + PFOS) was obtained from 3M Company (St. Paul, MN). The details of its purity (88.9%) and analytical characterization are described in Chang et al. 14 . PFOS dose formulation and analysisK + PFOS was prepared in vehicle (0.5% Tween 20 in deionized water) at either 0.3 μg/mL or 0.6 μg/mL; and with a daily dosing volume of 5 mL per kg body weight, it corresponded to a daily targeted dose of either 1.5 μg/kg body weight/day or 3 μg/kg body weight /day, respectively.The dosing solutions and the serum samples were analyzed for PFOS concentration by LC-MS/MS based on previous methods 14,15 . Briefly, matrix-matched standard curves were prepared and 18 O2-PFOS was used as internal standard for all extractions. All standards and samples underwent solid ...