Extracellular superoxide dismutase inhibits innate immune responses and clearance of an intracellular bacterial infection.
Extracellular superoxide dismutase inhibits innate immune responses and clearance of an intracellular bacterial infection.
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DOI：
10.4049/jimmunol.1102341
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发表时间：
2012-04-01
期刊：
影响因子：
--
通讯作者：
Berg RE
中科院分区：
文献类型：
--
作者：
Break TJ;Jun S;Indramohan M;Carr KD;Sieve AN;Dory L;Berg RE
活性氧氮(ROS/RNS)在细菌对病原体的免疫应答中起着重要作用。细胞外超氧化物歧化酶(EcSOD)调节细胞外ROS/RNS的浓度，有助于炎症损伤时的组织保护。因此，EcSOD参与免疫反应似乎是直观的，但人们对此知之甚少。在本研究中，我们利用不同水平的EcSOD活性的小鼠来研究这种酶在针对单核细胞增多性李斯特菌的免疫反应中的作用。令人惊讶的是，我们的数据表明，尽管中性粒细胞向肝脏募集增加，但EcSOD活性对宿主存活和细菌清除产生了负面影响。伴随着ECSOD活性增加的是中性粒细胞与细菌共处的减少，以及中性粒细胞凋亡的增加，这减少了总体和中性粒细胞特异性的肿瘤坏死因子-α的产生。与表达EcSOD的小鼠相比，缺乏EcSOD的小鼠的肝白细胞产生了等量的一氧化氮(NO·)。然而，在感染过程中，缺乏ECSOD的小鼠肝脏中的过氧亚硝酸根(NO3·−)水平高于表达ECSOD的小鼠。中性粒细胞耗竭研究表明，高水平的EcSOD活性导致中性粒细胞保护能力有限，而缺乏EcSOD的小鼠的中性粒细胞提供了比野生型小鼠的中性粒细胞更好的保护。综上所述，我们的数据表明，EcSOD活性降低了细菌感染期间的先天性免疫反应，并为治疗干预提供了一个潜在的靶点。
Reactive oxygen and nitrogen species (ROS/RNS) play important roles during immune responses to bacterial pathogens. Extracellular superoxide dismutase (ecSOD) regulates extracellular concentrations of ROS/RNS and contributes to tissue protection during inflammatory insults. The participation of ecSOD in immune responses seems therefore intuitive, yet is poorly understood. In the present study, we utilized mice with varying levels of ecSOD activity to investigate the involvement of this enzyme in immune responses against Listeria monocytogenes. Surprisingly, our data demonstrate that, despite enhanced neutrophil recruitment to the liver, ecSOD activity negatively impacted host survival and bacterial clearance. Increased ecSOD activity was accompanied by decreased co-localization of neutrophils with bacteria, as well as increased neutrophil apoptosis, which reduced overall and neutrophil-specific TNF-α production. Liver leukocytes from mice lacking ecSOD produced equivalent nitric oxide (NO·) when compared to mice expressing ecSOD. However, during infection, there were higher levels of peroxynitrite (NO3·−) in livers from mice lacking ecSOD compared to mice expressing ecSOD. Neutrophil depletion studies revealed that high levels of ecSOD activity resulted in neutrophils with limited protective capacity, whereas neutrophils from mice lacking ecSOD provided superior protection compared to neutrophils from wild-type mice. Taken together, our data demonstrate that ecSOD activity reduces innate immune responses during bacterial infection and provides a potential target for therapeutic intervention.
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影响因子：
5.5
作者：
Lorne, Emmanuel;Zmijewski, Jaroslaw W.;Abraham, Edward
通讯作者：
Abraham, Edward
影响因子：
4.8
作者：
Gao, Fei;Koenitzer, Jeffrey R.;Oury, Tim D.
通讯作者：
Oury, Tim D.
DOI：
10.1152/ajplung.00409.2001
发表时间：
2002-07-01
影响因子：
4.9
作者：
Ghio, AJ;Suliman, HB;Folz, RJ
通讯作者：
Folz, RJ
DOI：
10.1084/jem.20031051
发表时间：
2003-11-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Berg RE;Crossley E;Murray S;Forman J
通讯作者：
Forman J
影响因子：
4.4
作者：
Jaramillo, M;Olivier, M
通讯作者：
Olivier, M