全氟辛酸免疫毒性研究进展
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摘要
全氟辛酸(PFOA)是一种新型的持久性有机污染物,具有难降解性、生物蓄积性强及远距离环境迁移性等特点,近年来受到研究者的高度关注。PFOA会对机体的免疫系统产生毒性作用,结合近年来国内外关于PFOA免疫毒性的研究进展,本文主要综述了PFOA对小鼠、斑马鱼、猴等动物免疫器官的影响,对以自然杀伤细胞为代表的非特异性免疫功能的影响、对以体液免疫和细胞免疫为代表的特异性免疫功能的影响和以白介素家族为代表的免疫因子的影响,以及PFOA与溃疡性结肠炎、儿童哮喘及婴儿期免疫相关疾病等之间的关系,并进一步对PFOA可能引起的线粒体凋亡和干扰TNFα/NF-κB通路等免疫毒性作用机制进行总结。目前由于种属差异及研究资料的不确定性,PFOA免疫毒性表现相对复杂,因此系统深入地探究PFOA免疫毒性及其相关分子机制是未来研究方向之一;另外,模拟并研究真实环境中PFOA的长期慢性暴露水平,对于揭示PFOA对人类的真实风险更具有实际意义。
Perfluorooctanoic acid(PFOA) is a new type of persistent organic pollutant, and has been highly concerned by researchers in recent years due to its features such as degradationresistance, high bioaccumulation, and long-distance environmental migration. PFOA can produce toxic effects on the immune system. This paper reviewed the studied immune toxicities at home and abroad of PFOA to mice, zebrafish, and monkeys, including the nonspecific immune function of natural killer cells, specific immune function of humoral immunity and cellular immunity, and immune factors of interleukin family, and the relationships of PFOA with ulcerative colitis, childhood asthma, and infant immune related diseases. Furthermore, the possible mechanisms of mitochondrial apoptosis and TNFα/NF-κB pathway were summarized. The complex immune toxicities of PFOA due to species difference and the uncertainty of research data grant further research to systematically understand its immune toxicities and related molecular mechanisms; besides, it is of more practical significance in revealing the risk of PFOA to human beings by simulating and studying the long-term and chronic human exposure level in real life.
Perfluorooctanoic acid(PFOA) is a new type of persistent organic pollutant, and has been highly concerned by researchers in recent years due to its features such as degradationresistance, high bioaccumulation, and long-distance environmental migration. PFOA can produce toxic effects on the immune system. This paper reviewed the studied immune toxicities at home and abroad of PFOA to mice, zebrafish, and monkeys, including the nonspecific immune function of natural killer cells, specific immune function of humoral immunity and cellular immunity, and immune factors of interleukin family, and the relationships of PFOA with ulcerative colitis, childhood asthma, and infant immune related diseases. Furthermore, the possible mechanisms of mitochondrial apoptosis and TNFα/NF-κB pathway were summarized. The complex immune toxicities of PFOA due to species difference and the uncertainty of research data grant further research to systematically understand its immune toxicities and related molecular mechanisms; besides, it is of more practical significance in revealing the risk of PFOA to human beings by simulating and studying the long-term and chronic human exposure level in real life.
引文
[1]GOOSEY E,HARRAD S.Perfluoroalkyl compounds in dust from Asian,Australian,European,and north American homes and UK cars,classrooms,and offices[J].Environ Int,2011,37(1):86-92.
[2]LAU C,ANITOLE K,HODES C,et al.Perfluoroalkyl acids:a review of monitoring and toxicological findings[J].Toxicol Sci,2007,99(2):366-394.
[3]BENFORD D,DE BOER J,CARERE A,et al.Opinion of the scientific panel on contaminants in the food chain on perfluorooctane sulfonate(PFOS),perfluorooctanoic acid(PFOA)and their salts[J].EFSA J,2008,653:1-131.
[4]齐彦杰,周珍,史亚利,等.北京市市售鸡蛋和鸭蛋中全氟化合物的污染水平研究[J].环境科学,2013,34(1):244-250.
[5]孙红文.新型持久性有机污染物全氟烷基化合物分析方法与环境污染水平[C]//持久性有机污染物论坛2008暨第三届持久性有机污染物全国学术研讨会论文集.北京:中国化学会,中国环境科学学会,2008:25-26.
[6]SO M K,MIYAKE Y,YEUNG W Y,et al.Perfluorinated compounds in the Pearl River and Yangtze River of China[J].Chemosphere,2007,68(11):2085-2095.
[7]STEENLAND K,KUGATHASAN S,BARR D B.PFOA and ulcerative colitis[J].Environ Res,2018,165:317-321.
[8]MONDAL D,LOPEZ-ESPINOSA M J,ARMSTRONG B,et al.Relationships of perfluorooctanoate and perfluorooctane sulfonate serum concentrations between mother-child pairs in a population with perfluorooctanoate exposure from drinking water[J].Environ Health Perspect,2012,120(5):752-757.
[9]YANG Q,XIE Y,DEPIERRE J.Effects of peroxisome proliferators on the thymus and spleen of mice[J].Clin Exp Immunol,2000,122(2):219-226.
[10]王玉.全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)对BALB/c小鼠免疫系统毒性效应研究[D].武汉:华中农业大学,2011.
[11]方文迪.基于斑马鱼模型的全氟辛酸免疫毒效应及机理研究[D].杭州:杭州师范大学,2015.
[12]HAN Z,LIU Y,WU D,et al.Immunotoxicity and hepatotoxicity of PFOS and PFOA in tilapia(Oreochromis niloticus)[J].Chin J Chem,2012,31(4):424-430.
[13]GANNON S A,FASANO W J,MAWN M P,et al.Absorption,distribution,metabolism,excretion,and kinetics of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid ammonium salt following a single dose in rat,mouse,and cynomolgus monkey[J].Toxicology,2016,340:1-9.
[14]BUTENHOFF J,COSTA G,ELCOMBE C,et al.Toxicity of ammonium perfluorooctanoate in male cynomolgus monkeys after oral dosing for 6 months[J].Toxicol Sci,2002,69(1):244-257.
[15]BRIEGER A,BIENEFELD N,HASAN R,et al.Impact of perfluorooctanesulfonate and perfluorooctanoic acid on human peripheral leukocytes[J].Toxicol in Vitro,2011,25(4):960-968.
[16]YANG Q,ABEDI-VALUGERDI M,XIE Y,et al.Potent suppression of the adaptive immune response in mice upon dietary exposure to the potent peroxisome proliferator,perfluorooctanoic acid[J].Int Immunopharmacol,2002,2(2/3):389-397.
[17]DEWITT J C,COPELAND C B,STRYNAR M J,et al.Perfluorooctanoic acid-induced immunomodulation in adult C57BL/6J or C57BL/6N female mice[J].Environ Health Perspect,2008,116(5):644-650.
[18]FAIRLEY K J,PURDY R,KEARNS S,et al.Exposure to the immunosuppresant,perfluorooctanoic acid,enhances the murine igE and airway hyperreactivity response to ovalbumin[J].Toxicol Sci,2007,97(2):375-383.
[19]SINGH T S K,LEE S,KIM H H,et al.Perfluorooctanoic acid induces mast cell-mediated allergic inflammation by the release of histamine and inflammatory mediators[J].Toxicol Lett,2012,210(1):64-70.
[20]马伟慧,卢贺敏,叶乐平.全氟辛酸暴露对哮喘小鼠炎症介质IL-4和IFN-γ及糖皮质激素受体的影响[J].中国病理生理杂志,2018,34(2):352-357.
[21]YANG Q,XIE Y,ERIKSSON A M,et al.Further evidence for the involvement of inhibition of cell proliferation and development in thymic and splenic atrophy induced by the peroxisome proliferator perfluoroctanoic acid in mice[J].Biochem Pharmacol,2001,62(8):1133-1140.
[22]杨谨,李昂,杨谦,等.过氧化物酶体增殖剂PFOA对小鼠免疫系统的影响[J].细胞与分子免疫学杂志,2006,22(2):157-160.
[23]SON H Y,LEE S,TAK E N,et al.Perfluorooctanoic acid alters T lymphocyte phenotypes and cytokine expression in mice[J].Environ Toxicol,2009,24(6):580-588.
[24]QAZI M R,BOGDANSKA J,BUTENHOFF J L,et al.High-dose,short-term exposure of mice to perfluorooctanesulfonate(PFOS)or perfluorooctanoate(PFOA)affects the number of circulating neutrophils differently,but enhances the inflammatory responses of macrophages to lipopolysaccharide(LPS)in a similar fashion[J].Toxicology,2009,262(3):207-214.
[25]马佳乐,侯萍,王思瑶,等.全氟辛酸诱导斑马鱼脾脏损伤及白细胞介素表达紊乱的免疫毒效应研究[J].环境科学学报,2016,36(7):2687-2693.
[26]ZHANG H,FANG W,WANG D,et al.The role of interleukin fa m i l y i n p e r f l u o ro o c ta n o i c a c i d(P FOA)-i n d u c e d immunotoxicity[J].J Hazard Mater,2014,280:552-560.
[27]STEENLAND K,ZHAO L,WINQUIST A,et al.Ulcerative colitis and perfluorooctanoic acid(PFOA)in a highly exposed population of community residents and workers in the midOhio valley[J].Environ Health Perspect,2013,121(8):900-905.
[28]FEI C Y,MCLAUGHLIN J K,TARONE R E,et al.Fetal growth indicators and perfluorinated chemicals:a study in the Danish national birth cohort[J].Am J Epidemiol,2008,168(1):66-72.
[29]DONG G H,TUNG K Y,TSAI C H,et al.Serum polyfluoroalkyl concentrations,asthma outcomes,and immunological markers in a case control study of Taiwanese children[J].Environ Health Perspect,2013,121(4):507-513.
[30]OKADA E,SASAKI S,SAIJO Y,et al.Prenatal exposure to perfluorinated chemicals and relationship with allergies and infectious diseases in infants[J].Environ Res,2012,112:118-125.
[31]SHABALINA I G,PANARETAKIS T,BERGSTRAND A,et al.Effects of the rodent peroxisome proliferator and hepatocarcinogen,perfluorooctanoic acid,on poptosis in human hepatoma hepg2 cells[J].Carcinogenesis,1999,20(12):2237-2246.
[32]PANARETAKIS T,SHABALINA I G,GRANDéR D,et al.Reactive oxygen species and mitochondria mediate the induction of apoptosis in human hepatoma hepg2 cells by the rodent peroxisome proliferator and hepatocarcinogen,perfluorooctanoic acid[J].Toxicol Appl Pharmacol,2001,173(1):56-64.
[33]KLESZCZY?SKI K,STEPNOWSKI P,SK?ADANOWSKI A C.Mechanism of cytotoxic action of perfluorinated acids:II.Disruption of mitochondrial bioenergetics[J].Toxicol Appl Pharmacol,2009,235(2):182-190.
[34]YAO X,ZHONG L.Genotoxic risk and oxidative DNA damage in hepg2 cells exposed to perfluorooctanoic acid[J].Mutat Res,2005,587(1/2):38-44.
[35]姚晓峰,仲来福.全氟辛酸对HepG2细胞的遗传毒性及氧化性DNA损伤[J].毒理学杂志,2005,19(3):216-217.
[36]HAYDEN M S,GHOSH S.Shared principles in NF-κB signaling[J].Cell,2008,132(3):344-362.
[37]CORSINI E,AVOGADRO A,GALBIATI V,et al.In vitro evaluation of the immunotoxic potential of perfluorinated compounds(PFCS)[J].Toxicol Appl Pharmacol,2011,250(2):108-116.
[38]LIM W S,NG D L,KOR S B,et al.Tumour necrosis factor alpha down-regulates the expression of peroxisome proliferator activated receptor alpha(PPARα)in human hepatocarcinoma hepG2 cells by activation of NF-κBpathway[J].Cytokine,2013,61(1):266-274.
[39]STIENSTRA R,SAUDALE F,DUVAL C,et al.Kupffer cells promote hepatic steatosis via interleukin-1β-dependent suppression of peroxisome proliferator-activated receptorαactivity[J].Hepatology,2010,51(2):511-522.
[40]YANG Q,XIE Y,ALEXSON S E H,et al.Involvement of the peroxisome proliferator-activated receptor alpha in the immunomodulation caused by peroxisome proliferators in mice[J].Biochem Pharmacol,2002,63(10):1893-1900.
[41]LI K,GAO P,XIANG P,et al.Molecular mechanisms of PFOA-induced toxicity in animals and humans:Implications for health risks[J].Environ Internat,2017,99:43-54.
[2]LAU C,ANITOLE K,HODES C,et al.Perfluoroalkyl acids:a review of monitoring and toxicological findings[J].Toxicol Sci,2007,99(2):366-394.
[3]BENFORD D,DE BOER J,CARERE A,et al.Opinion of the scientific panel on contaminants in the food chain on perfluorooctane sulfonate(PFOS),perfluorooctanoic acid(PFOA)and their salts[J].EFSA J,2008,653:1-131.
[4]齐彦杰,周珍,史亚利,等.北京市市售鸡蛋和鸭蛋中全氟化合物的污染水平研究[J].环境科学,2013,34(1):244-250.
[5]孙红文.新型持久性有机污染物全氟烷基化合物分析方法与环境污染水平[C]//持久性有机污染物论坛2008暨第三届持久性有机污染物全国学术研讨会论文集.北京:中国化学会,中国环境科学学会,2008:25-26.
[6]SO M K,MIYAKE Y,YEUNG W Y,et al.Perfluorinated compounds in the Pearl River and Yangtze River of China[J].Chemosphere,2007,68(11):2085-2095.
[7]STEENLAND K,KUGATHASAN S,BARR D B.PFOA and ulcerative colitis[J].Environ Res,2018,165:317-321.
[8]MONDAL D,LOPEZ-ESPINOSA M J,ARMSTRONG B,et al.Relationships of perfluorooctanoate and perfluorooctane sulfonate serum concentrations between mother-child pairs in a population with perfluorooctanoate exposure from drinking water[J].Environ Health Perspect,2012,120(5):752-757.
[9]YANG Q,XIE Y,DEPIERRE J.Effects of peroxisome proliferators on the thymus and spleen of mice[J].Clin Exp Immunol,2000,122(2):219-226.
[10]王玉.全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)对BALB/c小鼠免疫系统毒性效应研究[D].武汉:华中农业大学,2011.
[11]方文迪.基于斑马鱼模型的全氟辛酸免疫毒效应及机理研究[D].杭州:杭州师范大学,2015.
[12]HAN Z,LIU Y,WU D,et al.Immunotoxicity and hepatotoxicity of PFOS and PFOA in tilapia(Oreochromis niloticus)[J].Chin J Chem,2012,31(4):424-430.
[13]GANNON S A,FASANO W J,MAWN M P,et al.Absorption,distribution,metabolism,excretion,and kinetics of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid ammonium salt following a single dose in rat,mouse,and cynomolgus monkey[J].Toxicology,2016,340:1-9.
[14]BUTENHOFF J,COSTA G,ELCOMBE C,et al.Toxicity of ammonium perfluorooctanoate in male cynomolgus monkeys after oral dosing for 6 months[J].Toxicol Sci,2002,69(1):244-257.
[15]BRIEGER A,BIENEFELD N,HASAN R,et al.Impact of perfluorooctanesulfonate and perfluorooctanoic acid on human peripheral leukocytes[J].Toxicol in Vitro,2011,25(4):960-968.
[16]YANG Q,ABEDI-VALUGERDI M,XIE Y,et al.Potent suppression of the adaptive immune response in mice upon dietary exposure to the potent peroxisome proliferator,perfluorooctanoic acid[J].Int Immunopharmacol,2002,2(2/3):389-397.
[17]DEWITT J C,COPELAND C B,STRYNAR M J,et al.Perfluorooctanoic acid-induced immunomodulation in adult C57BL/6J or C57BL/6N female mice[J].Environ Health Perspect,2008,116(5):644-650.
[18]FAIRLEY K J,PURDY R,KEARNS S,et al.Exposure to the immunosuppresant,perfluorooctanoic acid,enhances the murine igE and airway hyperreactivity response to ovalbumin[J].Toxicol Sci,2007,97(2):375-383.
[19]SINGH T S K,LEE S,KIM H H,et al.Perfluorooctanoic acid induces mast cell-mediated allergic inflammation by the release of histamine and inflammatory mediators[J].Toxicol Lett,2012,210(1):64-70.
[20]马伟慧,卢贺敏,叶乐平.全氟辛酸暴露对哮喘小鼠炎症介质IL-4和IFN-γ及糖皮质激素受体的影响[J].中国病理生理杂志,2018,34(2):352-357.
[21]YANG Q,XIE Y,ERIKSSON A M,et al.Further evidence for the involvement of inhibition of cell proliferation and development in thymic and splenic atrophy induced by the peroxisome proliferator perfluoroctanoic acid in mice[J].Biochem Pharmacol,2001,62(8):1133-1140.
[22]杨谨,李昂,杨谦,等.过氧化物酶体增殖剂PFOA对小鼠免疫系统的影响[J].细胞与分子免疫学杂志,2006,22(2):157-160.
[23]SON H Y,LEE S,TAK E N,et al.Perfluorooctanoic acid alters T lymphocyte phenotypes and cytokine expression in mice[J].Environ Toxicol,2009,24(6):580-588.
[24]QAZI M R,BOGDANSKA J,BUTENHOFF J L,et al.High-dose,short-term exposure of mice to perfluorooctanesulfonate(PFOS)or perfluorooctanoate(PFOA)affects the number of circulating neutrophils differently,but enhances the inflammatory responses of macrophages to lipopolysaccharide(LPS)in a similar fashion[J].Toxicology,2009,262(3):207-214.
[25]马佳乐,侯萍,王思瑶,等.全氟辛酸诱导斑马鱼脾脏损伤及白细胞介素表达紊乱的免疫毒效应研究[J].环境科学学报,2016,36(7):2687-2693.
[26]ZHANG H,FANG W,WANG D,et al.The role of interleukin fa m i l y i n p e r f l u o ro o c ta n o i c a c i d(P FOA)-i n d u c e d immunotoxicity[J].J Hazard Mater,2014,280:552-560.
[27]STEENLAND K,ZHAO L,WINQUIST A,et al.Ulcerative colitis and perfluorooctanoic acid(PFOA)in a highly exposed population of community residents and workers in the midOhio valley[J].Environ Health Perspect,2013,121(8):900-905.
[28]FEI C Y,MCLAUGHLIN J K,TARONE R E,et al.Fetal growth indicators and perfluorinated chemicals:a study in the Danish national birth cohort[J].Am J Epidemiol,2008,168(1):66-72.
[29]DONG G H,TUNG K Y,TSAI C H,et al.Serum polyfluoroalkyl concentrations,asthma outcomes,and immunological markers in a case control study of Taiwanese children[J].Environ Health Perspect,2013,121(4):507-513.
[30]OKADA E,SASAKI S,SAIJO Y,et al.Prenatal exposure to perfluorinated chemicals and relationship with allergies and infectious diseases in infants[J].Environ Res,2012,112:118-125.
[31]SHABALINA I G,PANARETAKIS T,BERGSTRAND A,et al.Effects of the rodent peroxisome proliferator and hepatocarcinogen,perfluorooctanoic acid,on poptosis in human hepatoma hepg2 cells[J].Carcinogenesis,1999,20(12):2237-2246.
[32]PANARETAKIS T,SHABALINA I G,GRANDéR D,et al.Reactive oxygen species and mitochondria mediate the induction of apoptosis in human hepatoma hepg2 cells by the rodent peroxisome proliferator and hepatocarcinogen,perfluorooctanoic acid[J].Toxicol Appl Pharmacol,2001,173(1):56-64.
[33]KLESZCZY?SKI K,STEPNOWSKI P,SK?ADANOWSKI A C.Mechanism of cytotoxic action of perfluorinated acids:II.Disruption of mitochondrial bioenergetics[J].Toxicol Appl Pharmacol,2009,235(2):182-190.
[34]YAO X,ZHONG L.Genotoxic risk and oxidative DNA damage in hepg2 cells exposed to perfluorooctanoic acid[J].Mutat Res,2005,587(1/2):38-44.
[35]姚晓峰,仲来福.全氟辛酸对HepG2细胞的遗传毒性及氧化性DNA损伤[J].毒理学杂志,2005,19(3):216-217.
[36]HAYDEN M S,GHOSH S.Shared principles in NF-κB signaling[J].Cell,2008,132(3):344-362.
[37]CORSINI E,AVOGADRO A,GALBIATI V,et al.In vitro evaluation of the immunotoxic potential of perfluorinated compounds(PFCS)[J].Toxicol Appl Pharmacol,2011,250(2):108-116.
[38]LIM W S,NG D L,KOR S B,et al.Tumour necrosis factor alpha down-regulates the expression of peroxisome proliferator activated receptor alpha(PPARα)in human hepatocarcinoma hepG2 cells by activation of NF-κBpathway[J].Cytokine,2013,61(1):266-274.
[39]STIENSTRA R,SAUDALE F,DUVAL C,et al.Kupffer cells promote hepatic steatosis via interleukin-1β-dependent suppression of peroxisome proliferator-activated receptorαactivity[J].Hepatology,2010,51(2):511-522.
[40]YANG Q,XIE Y,ALEXSON S E H,et al.Involvement of the peroxisome proliferator-activated receptor alpha in the immunomodulation caused by peroxisome proliferators in mice[J].Biochem Pharmacol,2002,63(10):1893-1900.
[41]LI K,GAO P,XIANG P,et al.Molecular mechanisms of PFOA-induced toxicity in animals and humans:Implications for health risks[J].Environ Internat,2017,99:43-54.