Potent suppression of the adaptive immune response in mice upon dietary exposure to the potent peroxisome proliferator, perfluorooctanoic acid

Potent suppression of the adaptive immune response in mice upon dietary exposure to the potent peroxisome proliferator, perfluorooctanoic acid
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DOI:
10.1016/s1567-5769(01)00164-3
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发表时间:
2002-02-01
影响因子:
5.6
通讯作者:
DePierre, JW
DePierre, JW
中科院分区:
医学2区
文献类型:
--
作者:
Yang, Q;Abedi-Valugerdi, M;DePierre, JW

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在以前的调查中,我们证明了严重的胸腺和脾脏萎缩发生在小鼠饮食暴露于几个强大的过氧化物酶体增殖物(PI)。在本研究中,有效的PP全氟辛酸(PFOA)对小鼠的适应性免疫的影响进行了评估,在体内和离体。研究的体内免疫反应涉及用马红细胞(HRBC)免疫小鼠,在用含全氟辛酸的饮食预处理10天后显示T细胞依赖性抗原。随后采用空斑形成细胞(PFC)试验和ELISA法测定抗体滴度,对原发性不道德反应进行定量。结果清楚地表明,口服PFOA可防止抗IgM和IgG抗体形成的空斑增加,以及这种免疫通常引起的IgM和IgG血清水平的增加。体外脾细胞增殖(测定为H-3-胸苷掺入)在T-和B-细胞激活剂的衰减与PFOA的饮食治疗,虽然类似的小鼠脾细胞与这种相同的化合物在体外治疗没有这样的效果。因此,相对代谢惰性的PP PFOA可以通过间接机制在小鼠中施加适应性免疫抑制。这种免疫抑制的可能相关性,在血浆脂质的变化所造成的PP进行了讨论。(C)2002 Elsevier Science B. V.保留所有权利。
In a previous investigation, we demonstrated that severe thymus and spleen atrophy occurs in mice upon dietary exposure to several potent peroxisome proliferators (PI's). In the present investigation, the effects of the potent PP perfluorooctanoic acid (PFOA) on the adaptive immunity of mice was evaluated both in vivo and ex vivo. The in vivo immune response examined involved immunization of mice with horse red blood cells (HRBCs), displaying T-cell-dependent antigens after pre-treatment with a PFOA-containing diet for 10 days. Subsequent quantitation of the primary Immoral response was performed employing both the plaque-forming cell (PFC) assay and determination of the antibody titer by ELISA. The results clearly demonstrate that oral administration of PFOA prevents both the increases in plaque formations by anti-IgM and -IgG and in serum levels of IgM and IgG normally evoked by such immunization. Ex vivo spleen cells proliferation (assayed as incorporation of H-3-thymidine) in response to both T- and B-cell activators was attenuated by dietary treatment with PFOA, although the analogous in vitro treatment of mouse spleen cells with this same compound had no such effects. Thus, the relatively metabolically inert PP PFOA may exert adaptive immunosuppression in mice by an indirect mechanism. The possible relevance of this immunosuppression to the alterations in plasma lipids caused by PPs is discussed. (C) 2002 Elsevier Science B.V. All rights reserved.