PRL2 Controls Phagocyte Bactericidal Activity by Sensing and Regulating ROS.
PRL2 Controls Phagocyte Bactericidal Activity by Sensing and Regulating ROS.
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PRL2 通过感知和调节 ROS 来控制吞噬细胞杀菌活性。
DOI：
10.3389/fimmu.2018.02609
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发表时间：
2018
影响因子：
7.3
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Yin C;Wu C;Du X;Fang Y;Pu J;Wu J;Tang L;Zhao W;Weng Y;Guo X;Chen G;Wang Z
虽然众所周知，炎症可增强白细胞杀菌活性，但其潜在机制尚不清楚。在此，我们报告了PRL2对炎症部位的氧化应激敏感。吞噬细胞中PRL2的减少会导致呼吸爆发活性增加，并增强吞噬细胞的杀菌活性。PRL2(磷酸酶再生肝2)在静息免疫细胞中高表达，但因炎症而显著下调。体外实验表明，PRL2对过氧化氢(H_2O_2)敏感，过氧化氢是炎症部位常见的损伤信号。作为对感染的反应，PRL2基因敲除(KO)吞噬细胞被高度激活，产生更多的活性氧(ROS)，并显示出增强的杀菌活性。髓细胞隔室中PRL2缺乏的小鼠对致死性李斯特菌感染具有抵抗力，并更快、更有效地清除细菌。此外，体外实验表明，PRL2与GTP酶Rac结合并调节ROS的产生。细菌感染后，RAC GTP酶在PRL2(KO)吞噬细胞中的活性高于野生型细胞。我们的发现表明，PRL2在炎症部位感知ROS，并调节吞噬细胞中ROS的产生。这种正反馈机制促进了吞噬细胞的杀菌活性，可能在先天抗菌免疫中发挥重要作用。
Although it is well-recognized that inflammation enhances leukocyte bactericidal activity, the underlying mechanisms are not clear. Here we report that PRL2 is sensitive to oxidative stress at inflamed sites. Reduced PRL2 in phagocytes causes increased respiratory burst activity and enhances phagocyte bactericidal activity. PRL2 (Phosphatase Regenerating Liver 2) is highly expressed in resting immune cells, but is markedly downregulated by inflammation. in vitro experiments showed that PRL2 was sensitive to hydrogen peroxide (H2O2), a common damage signal at inflamed sites. In response to infection, PRL2 knockout (KO) phagocytes were hyper activated, produced more reactive oxygen species (ROS) and exhibited enhanced bactericidal activity. Mice with PRL2 deficiency in the myeloid cell compartment were resistant to lethal listeria infection and cleared the bacteria more rapidly and effectively. Moreover, in vitro experiments demonstrated that PRL2 binds to GTPase Rac and regulates ROS production. Rac GTPases were more active in PRL2 (KO) phagocytes than in wild type cells after bacterium infection. Our findings indicate that PRL2 senses ROS at inflamed sites and regulates ROS production in phagocytes. This positive feedback mechanism promotes bactericidal activity of phagocytes and may play an important role in innate anti-bacterial immunity.
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影响因子：
--
作者：
Vázquez-Mendoza A;Carrero JC;Rodriguez-Sosa M
通讯作者：
Rodriguez-Sosa M
DOI：
10.1038/nri3423
发表时间：
2013-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.1216141110
发表时间：
2013-02-19
影响因子：
11.1
作者：
Kawazu, Masahito;Ueno, Toshihide;Mano, Hiroyuki
通讯作者：
Mano, Hiroyuki
影响因子：
4.8
作者：
Dong, Yuanshu;Zhang, Lujuan;Zhang, Zhong-Yin
通讯作者：
Zhang, Zhong-Yin
影响因子：
4
作者：
Al-Aidaroos, Abdul Qader O.;Zeng, Qi
通讯作者：
Zeng, Qi