Effects of environmentally-relevant levels of perfluorooctane sulfonate on clinical parameters and immunological functions in B6C3F1 mice.
Effects of environmentally-relevant levels of perfluorooctane sulfonate on clinical parameters and immunological functions in B6C3F1 mice.
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DOI：
10.3109/1547691x.2010.527868
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发表时间：
2011-01
影响因子：
3.3
通讯作者：
Peden-Adams MM
中科院分区：
文献类型：
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作者：
Fair PA;Driscoll E;Mollenhauer MA;Bradshaw SG;Yun SH;Kannan K;Bossart GD;Keil DE;Peden-Adams MM
在一系列研究的第一部分中，对全氟辛烷磺酸（PFOS）引起的小鼠绵羊红细胞特异性IgM抗体抑制进行了临床和免疫毒理学终点调查。成年雌性B6 C3 F1小鼠连续28天口服总剂量为0、0.1、0.5、1或5 mg PFOS/kg。与对照组相比，5 mg/kg剂量组的子宫湿重显著降低。未观察到消瘦综合征、营养不良、甲状腺稳态改变或明显毒性体征。脾脏CD 19 +/CD 21-、CD 19 +/CD 21+、B220+/CD 40+、CD 4 +/CD 154-、CD 4 +/CD 154+和MHC-II+细胞数量未发生变化。此外，体外抗CD 3或佛波酯肉豆蔻酸酯刺激的CD 4 + T细胞的体外IL-4、IL-5和IL-6产生不受影响。通过用抗CD 40或脂多糖体外刺激，B细胞的体外IL-6产生显著增加。B细胞产生的IL-6增加是评估的最敏感终点，导致抗CD 40刺激后最低测试剂量（0.1 mg/kg TAD）发生变化。需要开展进一步研究，以确定全氟辛烷磺酸在环境相关浓度下对炎症标志物（如IL-6）的影响，并确定与全氟辛烷磺酸诱导的IgM抑制相关的关键事件，以应对潜在的人类健康风险。
In the first part of a series of studies to account for perfluoroocatane sulfonate (PFOS)-induced sheep red blood cell (SRBC)-specific IgM antibody suppression in mice, a survey of clinical and immunotoxicological endpoints were examined. Adult female B6C3F1 mice were exposed orally for 28 days to a total administered dose of 0, 0.1, 0.5, 1, or 5 mg PFOS/kg. Uterus wet weight was significantly decreased compared to control at the 5 mg/kg dose. No indication of wasting syndrome, malnutrition, alteration of thyroid homeostasis, or signs of overt toxicity were observed. Numbers of splenic CD19+/CD21−, CD19+/CD21+, B220+/CD40+, CD4+/CD154−, CD4+/CD154+, and MHC-II+ cells were not altered. Additionally, ex vivo IL-4, IL-5, and IL-6 production by in vitro anti-CD3- or phorbol myristate acetate-stimulated CD4+ T-cells were not affected. Ex vivo IL-6 production by B-cells was significantly increased by in vitro stimulation with either anti-CD40 or lipopolysaccharide. Increased IL-6 production by B-cells was the most sensitive endpoint assessed resulting in alterations at the lowest dose tested (0.1 mg/kg TAD) following anti-CD40 stimulation. Further studies are required to characterize effects on inflammatory markers such as IL-6 at environmentally relevant concentrations of PFOS and to determine the key events associated with PFOS-induced IgM suppression to address potential human health risks.