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全氟壬酸(PFNA)对C57BL/6小鼠的急性免疫毒性作用

Acute Immunotoxic Effects of Perfluorononanoic Acid (PFNA) in C57BL/6 Mice.

作者信息

Rockwell Cheryl E, Turley Alexandra E, Cheng Xingguo, Fields Patrick E, Klaassen Curtis D

机构信息

Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824, USA.

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA.

出版信息

Clin Exp Pharmacol. 2013;Suppl 4. doi: 10.4172/2161-1459.S4-002.

Abstract

otrganic perfluorochemicals (PFCs) have become an environmental concern due to widespread detection in human blood and experimental evidence for immune, developmental, and liver toxicity. Whereas the blood concentrations of many PFCs are declining, blood levels of Perfluorononanoic Acid (PFNA) are rising in the United States. The purpose of the present studies was to determine the effects of PFNA on lymphoid organs and immune cells of C57BL/6 mice. The present study demonstrates that PFNA produces immunotoxic effects in both male and female C57BL/6 mice as evidenced by splenic atrophy, decreased splenocyte numbers, and a marked reduction in thymocyte viability. The current study also demonstrates that the effects of PFNA on different leukocyte populations are not uniform. The CD4CD8 double-positive thymocytes were particularly sensitive to PFNA in which the proportion of this population was >95% decreased relative to the entire CD4 thymocyte population in PFNA-treated mice. Interestingly, PFNA also markedly increased serum levels of TNFα in response to LPS in mice. Collectively, the present studies demonstrate that PFNA decreases lymphocyte viability and alters the immune response to LPS in C57BL/6 mice.

摘要

有机全氟化合物(PFCs)已成为一个环境问题,因为在人体血液中广泛检测到它们,并且有实验证据表明它们具有免疫、发育和肝脏毒性。尽管许多全氟化合物的血液浓度正在下降,但在美国,全氟壬酸(PFNA)的血液水平却在上升。本研究的目的是确定PFNA对C57BL/6小鼠淋巴器官和免疫细胞的影响。本研究表明,PFNA在雄性和雌性C57BL/6小鼠中均产生免疫毒性作用,表现为脾脏萎缩、脾细胞数量减少以及胸腺细胞活力显著降低。当前研究还表明,PFNA对不同白细胞群体的影响并不一致。CD4CD8双阳性胸腺细胞对PFNA特别敏感,在经PFNA处理的小鼠中,该群体相对于整个CD4胸腺细胞群体的比例下降超过95%。有趣的是,PFNA还显著增加了小鼠对脂多糖(LPS)反应时的血清TNFα水平。总体而言,本研究表明PFNA降低了C57BL/6小鼠的淋巴细胞活力,并改变了对LPS的免疫反应。

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