Impact of zinc metabolism on innate immune function in the setting of sepsis.
Impact of zinc metabolism on innate immune function in the setting of sepsis.
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DOI：
10.1024/0300-9831/a000034
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发表时间：
2010-10
影响因子：
2.3
通讯作者：
Liu, Ming-Jie
中科院分区：
文献类型：
--
作者：
Knoell, Daren L.;Liu, Ming-Jie
缺锌风险最高的个体（儿童、老年人、孕妇和哺乳期妇女、病态患者、酗酒者）感染的风险更高。虽然锌在维持适应性免疫中的重要作用是公认的，但对先天免疫系统的了解要少得多。我们最近报道，锌缺乏显着增加败血症动物模型的死亡率。特别是，缺锌小鼠清除细菌的能力降低，同时多个重要器官中NF-κ B介导的信号传导增加。这与急性期和先天免疫反应的夸大同时发生。值得注意的是，败血症患者也有类似的发现，即较低的血浆锌水平与更多的炎症和疾病严重程度增加有关。通过这些研究，我们一致地观察到，相对于其他锌转运蛋白，SLC 39 A8（Zip 8）是独特的，因为其表达在感染开始时被显著诱导。此外，诱导Zip 8介导的锌转运进入先天免疫细胞对于适当的免疫功能至关重要。Zip 8的功能是否超出了锌转运蛋白的传统作用仍在进行中，尽管新的证据表明Zip 8表达本身受NF-κB调节。总之，这些发现表明锌对适当的先天免疫功能至关重要，而hZip 8复杂地参与维持先天免疫防御。
Individuals at highest risk of zinc deficiency (children, elderly, pregnant and lactating women, morbidly ill, alcoholics) have a higher risk of infection. Whereas the essential role of zinc in maintaining adaptive immunity is well recognized, much less is known regarding the innate immune system. We recently reported that zinc deficiency significantly increases mortality in an animal model of sepsis. In particular, zinc-deficient mice had a decreased capacity to clear bacteria and a concomitant increase in NF-κB-mediated signaling across multiple vital organs. This occurred in tandem with exaggeration of the acute phase and innate immune response. Strikingly, sepsis patients revealed similar findings in that lower plasma zinc levels were associated with more inflammation and increased severity of illness. Through these investigations we have consistently observed that SLC39 A8 (Zip8) is unique, relative to other zinc transporters, in that its expression is significantly induced at the onset of infection. Moreover, induction of Zip8-mediated zinc transport into innate immune cells is vital for proper immune function. Whether Zip8 functions beyond the conventional role of a zinc transporter remains a work in progress, although new evidence has revealed that Zip8 expression itself is regulated by NF-κB. Taken together, these findings indicate that zinc is vital for proper innate immune function and that hZip8 is intricately involved in maintaining innate immune defense.
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影响因子：
4.2
作者：
King, JC;Shames, DM;Woodhouse, LR
通讯作者：
Woodhouse, LR
影响因子：
4.4
作者：
Haase, Hajo;Ober-Bloebaum, Julia L.;Rink, Lothar
通讯作者：
Rink, Lothar
影响因子：
4.2
作者：
Black, RE
通讯作者：
Black, RE
DOI：
10.1073/pnas.0510407103
发表时间：
2006-02-07
影响因子：
11.1
作者：
Aydemir, TB;Blanchard, RK;Cousins, RJ
通讯作者：
Cousins, RJ
影响因子：
8.8
作者：
Abraham, Edward;Singer, Mervyn
通讯作者：
Singer, Mervyn