Neutrophil extracellular traps promote deep vein thrombosis in mice.
Neutrophil extracellular traps promote deep vein thrombosis in mice.
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DOI：
10.1111/j.1538-7836.2011.04544.x
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Wagner DD
中科院分区：
文献类型：
--
作者：
Brill A;Fuchs TA;Savchenko AS;Thomas GM;Martinod K;De Meyer SF;Bhandari AA;Wagner DD
在激活时，中性粒细胞可以释放称为中性粒细胞胞外陷阱（NETs）的核物质，最初被描述为抗菌防御的一部分。细胞外染色质在体外具有促血栓形成作用，并在实验性深静脉血栓形成（DVT）狒狒的血浆和血栓中蓄积。探讨细胞外染色质在深静脉血栓形成中的来源和作用。我们使用了一个建立的小鼠模型的DVT诱导的血流限制（狭窄）在下腔静脉（IVC）。我们证明，细胞外DNA的水平增加后6小时下腔静脉狭窄的血浆中，相比假手术小鼠。免疫组织化学染色显示血栓的红色（富含RBC）和白色（富含血小板）部分均存在Gr-1阳性中性粒细胞。瓜氨酸化组蛋白H3（CitH 3）是NET结构的一个组成部分，仅存在于血栓的红色部分，并且经常与Gr-1抗原相关。血栓的免疫荧光染色显示细胞外CitH 3和血管性血友病因子（VWF），血小板粘附分子在该模型中血栓的发展至关重要的接近。输注脱氧核糖核酸酶1（DNase 1）可保护小鼠在6 h后免于DVT，也可保护48 h后免于IVC狭窄。输注小牛胸腺组蛋白的未分级混合物增加了血浆VWF，并在狭窄应用后早期促进DVT。细胞外染色质，可能来源于中性粒细胞，是静脉血栓的结构部分，DNA支架和组蛋白似乎有助于小鼠DVT的发病机制。NET可能为DVT药物开发提供新的靶点。
Upon activation, neutrophils can release nuclear material known as neutrophil extracellular traps (NETs), which were initially described as a part of antimicrobial defense. Extracellular chromatin was recently reported to be pro-thrombotic in vitro and to accumulate in plasma and thrombi of baboons with experimental deep vein thrombosis (DVT). To explore the source and role of extracellular chromatin in DVT. We used an established murine model of DVT induced by flow restriction (stenosis) in the inferior vena cava (IVC). We demonstrate that the levels of extracellular DNA increase in plasma after 6 h IVC stenosis, compared to sham-operated mice. Immunohistochemical staining revealed the presence of Gr-1-positive neutrophils in both red (RBC-rich) and white (platelet-rich) parts of thrombi. Citrullinated histone H3 (CitH3), an element of NETs’ structure, was present only in the red part of thrombi and was frequently associated with the Gr-1 antigen. Immunofluorescent staining of thrombi showed proximity of extracellular CitH3 and von Willebrand factor (VWF), a platelet adhesion molecule crucial for thrombus development in this model. Infusion of Deoxyribonuclease 1 (DNase 1) protected mice from DVT after 6 h and also 48 h IVC stenosis. Infusion of an unfractionated mixture of calf thymus histones increased plasma VWF and promoted DVT early after stenosis application. Extracellular chromatin, likely originating from neutrophils, is a structural part of a venous thrombus and both the DNA scaffold and histones appear to contribute to the pathogenesis of DVT in mice. NETs may provide new targets for DVT drug development.
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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
DOI：
10.1073/pnas.90.3.1004
发表时间：
1993-02-01
影响因子：
11.1
作者：
DAHLBACK, B;CARLSSON, M;SVENSSON, PJ
通讯作者：
SVENSSON, PJ
影响因子：
4.3
作者：
Myers, DD;Hawley, AE;Wakefield, TW
通讯作者：
Wakefield, TW
影响因子：
4.1
作者：
Gamberucci, A;Fulceri, R;Benedetti, A
通讯作者：
Benedetti, A
影响因子：
20.3
作者：
Brooks, Erin G.;Trotman, Winifred;Bovill, Edwin G.
通讯作者：
Bovill, Edwin G.