Suppression of Humoral Immunity in Mice following Exposure to Perfluorooctane Sulfonate

Abstract

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. Natural killer cell activity was increased compared with 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 (PFC) response was suppressed in male mice beginning at 0.05 mg/kg TAD and in females at 0.5 mg/kg TAD. Serum trinitrophenyl (TNP)-specific IgM titers were also decreased by PFOS after TNP-LPS (TNP conjugated to lipopolysacharide) challenge suggesting that the humoral immune effects may be attributed to the B-cell rather than T-cell because both T-dependent (SRBC) and T-independent (TI) (TNP-LPS) antigens result in suppressed IgM production. Based on the PFC response, the low observed effect level (LOEL) for males was 0.05 mg/kg TAD (ED(50) = 0.021 mg/kg TAD) and for females was 0.5 mg/kg TAD (ED(50) = 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-cells as a potential target.

Type 1 and Type 2 cytokines imbalance in adult male C57BL/6 mice following a 7-day oral exposure to perfluorooctanesulfonate (PFOS)

“…Our studies, as well as those of other investigators, have shown that these compounds can activate certain components of innate immunity (Qazi et al, 2009a) but suppress acquired immunity (Yang et al, 2000(Yang et al, , 2001(Yang et al, , 2002aDewitt et al, 2008;Peden-Adams et al, 2008;Dong et al, 2009;Qazi et al, 2009b;Zheng et al, 2009). For instance, 7-10 days of dietary or gavage exposure of mice to either PFOS or perfluorooctanoate (PFOA) causes severe atropy of the thymus (central organ) and spleen (peripheral organ), two important immune organs for acquired immune responses (Yang et al, 2000(Yang et al, , 2001(Yang et al, , 2002aQazi et al, 2009b).…”

“…At the same time, the populations of splenocytes and thymocytes of all phenotypes are reduced dramatically in size. With both compounds, the reduction in splenic cellularity is associated with a significant reduction in specific humoral immune responses against foreign antigens, e.g., horse or sheep red blood cells (Yang et al, 2002a;Peden-Adams et al, 2008;Dong et al, 2009;Zheng et al, 2009). …”

Suppression of antigen-specific antibody responses in mice exposed to perfluorooctanoic acid: Role of PPARαand T- and B-cell targeting

“…To better understand the role of PPAR in suppression of the TDAR in mice and to improve the rodent data for applicability to potential immunotoxicological risk for humans exposed to PFOA, experiments were conducted to determine if suppression of the TDAR in rodents is dependent on PPAR ligation. Effects of PFOA exposure on the TIAR were also investigated because the structurally-related compound perfluorooctane sulfonate (PFOS) was reported to inhibit antibody responses by targeting B-cells (Peden-Adams et al, 2008). The T-helper cell-independent (i.e.…”

“…This focus was based on a set of papers by Yang et al (2000Yang et al ( , 2001Yang et al ( , 2002b) that indicated reductions in relative spleen and thymus weights and suppression of the T-cell-dependant antibody response (TDAR). Succeeding studies of PFOA and related PFAS (PFOA, PFOS, and ammonium perfluorooctanoate [APFO, a precursor compound to PFOA]) also demonstrated suppression of the TDAR (DeWitt et al, 2008;Loveless et al, 2008) and that exposure to PFOS also affected the T-cell-independent antibody response (TIAR; Peden-Adams et al, 2008). Suppression of both the TDAR and TIAR suggests that B-cells are targeted by PFAS.…”

Persistent organic pollutants and haematological markers in Greenlandic pregnant women: the ACCEPT sub-study

“…High serum POP levels in humans in the Arctic area have been related to age, marine food intake and smoking rate [2]. The toxic and immunomodulatory effects of POPs have previously been investigated, especially in relation to polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and perfluoroalkylated substances (PFASs) [3–5]. In addition, previous studies have reported the effects of POP exposure on the immune system in laboratory animals and humans, especially in connection with depressed immunity and reduced vaccination response [6–12].…”