title: Suppression of antigen-specific antibody responses in mice exposed to perfluorooctanoic acid: Role of PPARα and T- and B-cell targeting.
abstract: T-cell-dependent antibody responses (TDAR) are suppressed in female C57BL/6N mice exposed to ≥3.75 mg/kg of perfluorooctanoic acid (PFOA) for 15 days. To determine if suppression of humoral immunity by PFOA is peroxisome proliferator activated receptor alpha (PPARα)-dependent and if suppression is associated with specific targeting of T- or B-cells, three separate experiments were conducted: (1) female PPARα constitutive knockout (PPARα KO; B6.129S4-Ppar(tm1Gonz)N12) and wild-type controls (WT; C57BL/6-Tac) exposed to 0, 7.5, or 30 mg PFOA/kg for 15 days were immunized on Day 11 with a T-cell-dependent antigen and sera then collected for measures of antigen-specific IgM titers (TDAR) 5 days later; (2) female C57BL/6N WT mice exposed to 0, 0.94, 1.88, 3.75, or 7.5 mg PFOA/kg for 15 days were immunized with a T-cell-independent antigen on Day 11 and sera were then collected for analyses of antigen-specific IgM titers (TIAR) 7 days later; and (3) splenic lymphocyte phenotypes were assessed in unimmunized female C57BL/6N WT mice exposed to 0, 3.75, or 7.5 mg PFOA/kg for 10 days to investigate effects of PFOA in the absence of specific immunization. Separate groups of mice were immunized with a T-cell-dependent antigen after 11 days of exposure and splenic lymphocyte sub-populations were assessed after 13 or 15 days of exposure to assess numbers of stimulated cells. The results indicated that exposure to ≥1.88 mg PFOA/kg suppressed the TIAR; exposure to 30 mg PFOA/kg suppressed the TDAR in both PPARα KO and WT mice. The percentage of splenic B-cells was unchanged. Results obtained in the PPARα KO mice indicated that PPARα suppression of TDAR was independent of PPARα involvement. Suppression of the TIAR and the TDAR with minimal lymphocyte sub-population effects suggested that effects on humoral immunity are likely mediated by disruption of B-cell/plasma cell function.
authors.affiliation: a Department of Pharmacology and Toxicology , Brody School of Medicine, East Carolina University , Greenville , NC , USA .
authors.forename: Jamie C
authors.initials: JC
authors.lastname: DeWitt
authors.affiliation: b Cardiopulmonary and Immunotoxicology Branch, Environmental Public health Division, NHEERL, U.S. Environmental Protection Agency , Research Triangle Park , NC , and.
authors.forename: Wanda C
authors.initials: WC
authors.lastname: Williams
authors.affiliation: c Department of Biology , East Carolina University , Greenville , NC , USA.
authors.forename: N Jonathan
authors.initials: NJ
authors.lastname: Creech
authors.affiliation: b Cardiopulmonary and Immunotoxicology Branch, Environmental Public health Division, NHEERL, U.S. Environmental Protection Agency , Research Triangle Park , NC , and.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Luebke
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002210:Caprylates / Q000633:toxicity*; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D007114:Immunization; D007075:Immunoglobulin M / Q000097:blood; D007165:Immunosuppression Therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D019064:Product Packaging; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; D007075:Immunoglobulin M; D047493:PPAR alpha; C023036:perfluorooctanoic acid
keywords: PFOA; PPARα; TDAR; TIAR