PAD4-mediated neutrophil extracellular trap formation is not required for immunity against influenza infection.
PAD4-mediated neutrophil extracellular trap formation is not required for immunity against influenza infection.
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DOI：
10.1371/journal.pone.0022043
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Mowen KA
中科院分区：
文献类型：
--
作者：
Hemmers S;Teijaro JR;Arandjelovic S;Mowen KA
在炎症反应中，中性粒细胞迁移到感染部位，通过吞噬、分泌抗微生物介质或释放中性粒细胞胞外陷阱(Net)来杀死入侵的病原体。Net是一种专门的抗微生物结构，由去凝集的染色质装饰着杀菌剂组成。在慢性肺炎性疾病囊性纤维化患者中，发现Net的数量增加，这与肺梗阻的严重程度有关。此外，甲型流感感染期间的急性肺部炎症的特点是中性粒细胞大量涌入肺部。Nets在病毒介导的肺部炎症中的作用尚不清楚。组蛋白H3和H4的组蛋白H3和H4在PAD4介导的脱亚胺作用下形成网状结构是必需的。因此，我们产生了一种PAD4缺陷小鼠品系，该品系具有显著的不能形成Net的能力。这些小鼠感染了A/WSN流感病毒，并从白细胞肺渗透、肺病理、病毒复制、体重减轻和死亡率等水平进行监测。在测试的所有参数中，PAD4 KO的表现与WT小鼠相似，但它们在感染期间表现出轻微的、但在统计学上不同的体重减轻动力学，这并未反映在提高存活率上。总体而言，我们得出结论，在甲型流感感染的小鼠模型中，PAD4介导的网络形成是必要的。
During an inflammatory response, neutrophils migrate to the site of infection where they can kill invading pathogens by phagocytosis, secretion of anti-microbicidal mediators or the release of neutrophil extracellular traps (NETs). NETs are specialized anti-microbial structures comprised of decondensed chromatin decorated with microbicidal agents. Increased amount of NETs have been found in patients suffering from the chronic lung inflammatory disease cystic fibrosis, correlating with increased severity of pulmonary obstruction. Furthermore, acute lung inflammation during influenza A infection is characterized by a massive influx of neutrophils into the lung. The role of NETs during virus-mediated lung inflammation is unknown. Peptidylarginine deiminase 4 (PAD4)-mediated deimination of histone H3 and H4 is required for NET formation. Therefore, we generated a PAD4-deficient mouse strain that has a striking inability to form NETs. These mice were infected with influenza A/WSN, and the disease was monitored at the level of leukocytic lung infiltration, lung pathology, viral replication, weight loss and mortality. PAD4 KO fared comparable to WT mice in all the parameters tested, but they displayed slight but statistically different weight loss kinetics during infection that was not reflected in enhanced survival. Overall, we conclude that PAD4-mediated NET formation is dispensable in a mouse model of influenza A infection.
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DOI：
10.1084/jem.20100239
发表时间：
2010-08-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Li P;Li M;Lindberg MR;Kennett MJ;Xiong N;Wang Y
通讯作者：
Wang Y
小鼠流感病毒感染期间中性粒细胞在上呼吸道和下呼吸道中的作用。
影响因子：
5.8
作者：
Tate, Michelle D.;Brooks, Andrew G.;Reading, Patrick C.
通讯作者：
Reading, Patrick C.
DOI：
10.1073/pnas.0401901101
发表时间：
2004-05-04
影响因子：
11.1
作者：
Lindemann, SW;Yost, CC;Zimmerman, GA
通讯作者：
Zimmerman, GA
脊髓细胞细胞募集会导致急性病毒性脑膜炎期间致命的中枢神经系统损伤。
影响因子：
64.8
作者：
Kim, Jiyun V.;Kang, Silvia S.;Dustin, Michael L.;McGavern, Dorian B.
通讯作者：
McGavern, Dorian B.
影响因子：
5.8
作者：
Chang X;Fang K
通讯作者：
Fang K