ToxSci Advance Access published online on March 20, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn059
SUPPRESSION OF HUMORAL IMMUNITY IN MICE FOLLOWING EXPOSURE TO PERFLUOROOCTANE SULFONATE (PFOS)
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Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA
Department of Medicine/Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC, USA
Marine Biomedicine and Environmental Science Center, Medical University of South Carolina, Charleston, SC, USA
National Institute of Standards and Technology, Hollings Marine Laboratory, Charleston, SC, USA
¶ Clinical Laboratory Sciences, University of Nevada Las Vegas, Las Vegas NV, USA
| Medical Research Service, Ralph Johnson VAMC, Charleston, SC, USA
* Author to Whom Correspondence should be addressed: Margie M. Peden-Adams, Ph.D., MUSC, 221 Ft. Johnson Rd., Charleston, SC 29412, Phone: 843-762-8551, Fax: 843-762-8700, Email: pedenada{at}musc.edu, Email: pedenadams{at}hotmail.com
Received January 25, 2008; revision received March 6, 2008; accepted March 6, 2008
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Abstract |
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Adult male and female B6C3F1 mice were exposed to perfluorooctane sulfonate (PFOS) daily via gavage for 28 days (0, 0.005, 0.05, 0.1, 0.5, 1 or 5 mg/kg total administered dose [TAD]). Following exposure, various immune parameters were assessed and serum PFOS concentrations were determined. Lymphocyte proliferation was not altered in either gender. NK-cell activity was increased compared to control at 0.5, 1, and 5 mg/kg TAD in male mice but was not altered in female mice. At these treatment levels, splenic T-cell immunophenotypes were minimally altered in females, but all T-cell subpopulations were significantly modulated in males beginning at 0.1 mg/kg TAD. The sheep red blood cell (SRBC) plaque-forming cell response (PFC) was suppressed in male mice beginning at 0.05 mg/kg TAD and in females at 0.5 mg/kg TAD. Serum TNP-specific IgM titers were also decreased by PFOS after TNP-LPS challenge suggesting that the humoral immune effects may be attributed to the B-cell rather than T-cell since both T-dependent (SRBC) and T-independent (TNP-LPS) antigens result in suppressed IgM production. Based on the PFC response, the LOEL for males was 0.05 mg/kg TAD [ED50 = 0.021 mg/kg TAD] and for females was 0.5 mg/kg TAD [ED50 = 0.59 mg/kg TAD]. Measured PFOS serum concentrations at these dose levels were 91.5 + 22.2 ng/g and 666 + 108 ng/g (mean + SD), respectively. The male LOEL serum level was approximately 14-fold lower than reported mean blood levels from occupationally exposed humans and fell in the upper range of concentrations reported for the general population. Overall, this study provides a profile of PFOS immunotoxicity showing effects at levels reported in humans and identifies the B-cell as a potential target.
Key Words: PFOS; immunotoxicity; immune; humoral immunity; PFC assay; TNP-LPS; serum levels.