Role of transferrin, transferrin receptors, and iron in macrophage listericidal activity.

Role of transferrin, transferrin receptors, and iron in macrophage listericidal activity.
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DOI:
10.1084/jem.174.2.459
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发表时间:
1991-08-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Campbell PA
Campbell PA
中科院分区:
其他
文献类型:
--
作者:
Alford CE;King TE Jr;Campbell PA

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目前还不知道是什么性质区分巨噬细胞可以杀死兼性细胞内细菌,如李斯特菌,从那些不能。李斯特菌是一种需要铁生长的生物体,但巨噬细胞杀李斯特菌机制也可能是铁依赖性的。我们在这里表明,居民腹腔巨噬细胞和巯基乙酸引起的巨噬细胞不能杀死大肠杆菌,但蛋白酶胨引起的和FCS引起的巨噬细胞可以。所有这些细胞群都吞噬巨噬细胞。转铁蛋白受体表达在常驻细胞上低,在蛋白胨和FCS诱导的细胞上居中,在巯基乙酸盐诱导的细胞上高。转铁蛋白通过转铁蛋白受体将铁转运到细胞中:因此,驻留细胞的铁含量低,蛋白胨和FCS诱导的细胞的铁含量中等,巯基乙酸盐诱导的细胞的铁含量高。此外,转铁蛋白的抗体,阻止它结合其受体,抑制杀李斯特菌的巨噬细胞杀死这种细菌。最后,具有高转铁蛋白受体表达和高细胞内铁的非杀李斯特菌细胞如果与脱铁转铁蛋白(一种阻止细胞摄取铁的无铁配体)孵育则成为杀李斯特菌的。这些数据表明,巨噬细胞必须有足够的细胞内铁来支持杀李斯特菌机制,但太多的铁有利于细菌的生长,而细菌不再能被巨噬细胞杀死。
It is not yet known what properties distinguish macrophages which can kill facultative intracellular bacteria, such as Listeria monocytogenes, from those which cannot. Listeria is an organism which requires iron for growth, yet macrophage listericidal mechanisms are also likely to be iron dependent. We show here that resident peritoneal macrophages and thioglycollate-elicited macrophages cannot kill listeria, but proteose peptone-elicited and FCS-elicited macrophages can. All these cell populations phagocytose listeria. Transferrin receptor expression is low on resident cells, intermediate on peptone- and FCS-elicited cells, and high on thioglycollate-elicited cells. Transferrin transports iron into cells via the transferrin receptor: thus, iron content of resident cells is low, of peptone- and FCS- elicited cells is intermediate, and of thioglycollate-elicited cells is high. Moreover, antibody to transferrin, which prevents it binding its receptor, inhibits listericidal macrophages from killing this bacterium. Finally, nonlistericidal cells with high transferrin receptor expression and high intracellular iron become listericidal if they are incubated with apotransferrin, an iron-free ligand which prevents iron uptake by cells. These data suggest that macrophages must have enough available intracellular iron to support listericidal mechanisms, but too much iron favors growth of the bacterium, which no longer can be killed by the macrophage.