Expression and function of cystine/glutamate transporter in neutrophils
Expression and function of cystine/glutamate transporter in neutrophils
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DOI：
10.1189/jlb.0606385
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发表时间：
2007-04
影响因子：
5.5
通讯作者：
Y. Sakakura;Hideyo Sato;Ayako Shiiya;M. Tamba;J. Sagara;M. Matsuda;N. Okamura;N. Makino;S. Bannai
中科院分区：
文献类型：
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作者：
Y. Sakakura;Hideyo Sato;Ayako Shiiya;M. Tamba;J. Sagara;M. Matsuda;N. Okamura;N. Makino;S. Bannai
由中性粒细胞产生的活性氧（ROS）在宿主防御感染中是必不可少的，但可能对中性粒细胞本身有害。谷胱甘肽（GSH）在保护细胞免受ROS介导的氧化损伤中起着关键作用。胱氨酸/谷氨酸转运蛋白，称为系统xc-，由两种蛋白质xCT和4F 2 hc组成，对维持哺乳动物培养细胞中的GSH水平很重要。本文研究了中性粒细胞中的XC-系统。在人外周血中性粒细胞，无论是系统xc-或xCT mRNA的活性检测。体外培养时，细胞活性被诱导，表达xCT mRNA。在酵母多糖或PMA的调理下，mRNA的表达明显增强。相比之下，小鼠腹膜渗出液中性粒细胞，制备后立即，表现出系统xc-活性和表达xCT mRNA。培养后活性和表达量进一步提高。来自xCT-缺陷（xCT-/-）小鼠的腹膜渗出液细胞（主要是中性粒细胞）的半胱氨酸含量低于野生型小鼠。xCT−/−细胞中的GSH水平在培养过程中迅速下降，而野生型细胞中的GSH水平在培养过程中保持不变。与野生型细胞相比，xCT−/−细胞在培养中诱导的细胞凋亡增强。这些结果表明，系统xc-起着重要的作用，在中性粒细胞被激活时，他们的GSH消耗加快。
Reactive oxygen species (ROS) produced by neutrophils are essential in the host defense against infections but may be harmful to neutrophils themselves. Glutathione (GSH) plays a pivotal role in protecting cells against ROS‐mediated oxidant injury. Cystine/glutamate transporter, designated as system xc– and consisting of two proteins, xCT and 4F2hc, is important to maintain GSH levels in mammalian‐cultured cells. In the present paper, we have investigated system xc– in neutrophils. In human peripheral blood neutrophils, neither the activity of system xc– nor xCT mRNA was detected. The activity was induced, and xCT mRNA was expressed when they were cultured in vitro. The mRNA expression was much enhanced in the presence of opsonized zymosan or PMA. In contrast, mouse peritoneal exudate neutrophils, immediately after preparation, exhibited system xc– activity and expressed xCT mRNA. The activity and the expression were heightened further when they were cultured. Peritoneal exudate cells (mostly neutrophils) from xCT‐deficient (xCT−/−) mice had lower cysteine content than those from the wild‐type mice. GSH levels in the xCT−/−cells decreased rapidly when they were cultured, whereas those in the wild‐type cells were maintained during the culture. Apoptosis induced in culture was enhanced in the xCT−/−cells compared with the wild‐type cells. These results suggest that system xc– plays an important role in neutrophils when they are activated, and their GSH consumption is accelerated.