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IMMUNE FUNCTION IN INTACT AND PPARΑ KNOCKOUT MICE EXPOSED TO PFOA
DEWITT, J., C. B. COPELAND, AND R. W. LUEBKE. IMMUNE FUNCTION IN INTACT AND PPARΑ KNOCKOUT MICE EXPOSED TO PFOA. Presented at Society of Toxicology Annual Meeting, Seattle, WA, March 16 - 20, 2008.
To study immune function in intact and PPARA knockout mice exposed to PFOA.
Perfluorooctanoic acid (PFOA), used in fluoropolymer production, is environmentally persistent, present in human and wildlife populations worldwide, and associated with health effects in laboratory animals, including immunomodulation. PFOA toxicity may be mediated by the peroxisome proliferator activated receptor alpha (PPARα). Lymphoid tissues of mice deficient in PPARα (KO) were reported to be less susceptible to PFOA than wild-type (WT) mice. We therefore exposed Sv129 or C57BL/6 PPARα KO and WT mice to 0-30 mg PFOA/kg BW in drinking water for 15d. On d11 of dosing, mice were i.v. immunized with sheep red blood cells (SRBCs). Serum for evaluation of IgM titers was collected 1d post-dosing (PD). Booster immunizations were given 10d PD; serum for evaluation of IgG titers was collected 15d PD. In Sv129 mice, IgG titers were similar in dosed and control groups in Sv129s; IgM titers were statistically elevated in KOs (30 mg/kg) relative to controls and unaffected in WTs. In C57BL/6 mice, IgM titers were statistically suppressed in WTs and KOs exposed to 30 mg/kg relative to controls; IgG titers were not altered. PFOA did not alter lymphoid organ weights in WT or KO Sv129 or KO C57BL/6 mice; however, spleen weights were statistically reduced in C57BL/6 WTs, when evaluated 1d PD. Absolute and relative liver weights were statistically increased in all exposed groups. Sensitivity to PFOA, based on liver weight increases, was Sv129 WT > Sv129 KO > C57BL/6 WT > C57BL/6 KO. However, based on alteration of IgM titers, sensitivity to PFOA was C57BL/6 WT > C57BL/6 KO > Sv129 KO > Sv129 WT. This difference suggests that strain sensitivity to PFOA and non-PPARα mechanisms influence liver weights and antibody synthesis. In a separate study, IgM titers were statistically reduced in adrenalectomized C57BL/6 WTs relative to controls, thus minimizing a central role for stress-induced corticosterone release as the prime driver for reduced antibody synthesis. (This abstract does not reflect EPA policy and was supported by UNC/EPA Cooperative Training Agreement CT829472.)
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
EXPERIMENTAL TOXICOLOGY DIVISION