Neutrophil extracellular trap-microparticle complexes enhance thrombin generation via the intrinsic pathway of coagulation in mice.
Neutrophil extracellular trap-microparticle complexes enhance thrombin generation via the intrinsic pathway of coagulation in mice.
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DOI：
10.1038/s41598-018-22156-5
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发表时间：
2018-03-05
影响因子：
4.6
通讯作者：
Thorlacius H
中科院分区：
文献类型：
--
作者：
Wang Y;Luo L;Braun OÖ;Westman J;Madhi R;Herwald H;Mörgelin M;Thorlacius H
腹腔脓毒症与止血功能障碍有关。凝血酶生成（TG）是全身凝血的限速步骤。中性粒细胞可以排出中性粒细胞胞外陷阱（NET）和/或微粒（MP），尽管它们在病理性凝血中的作用仍然难以捉摸。盲肠结扎和穿刺（CLP）诱导的TG在体内反映了从脓毒症动物的血浆产生凝血酶的能力降低。中性粒细胞的消耗增加了CLP小鼠血浆中的TG。脓毒症与中性粒细胞中组蛋白3瓜氨酸和血浆游离DNA和DNA-组蛋白复合物水平升高有关，给予DNA酶不仅消除了NET形成，而且还升高了脓毒症中的TG。分离的NET增加TG和与DNA酶共孵育废除NET诱导的凝血酶形成。NET触发的TG被阻断因子XII抑制，在因子XII缺乏的血浆中被消除，但在因子VII缺乏的血浆中完好无损。中性粒细胞的活化同时产生大量的嗜中性粒细胞衍生的MP，发现其通过组蛋白-磷脂酰丝氨酸相互作用与NET结合。这些研究结果表明，第一次NET和MP物理相互作用，NET可能构成一个功能组装平台的MP。我们的结论是，NET-MP复合物诱导TG通过内源性途径的凝血和嗜中性粒细胞衍生的MP发挥关键作用NET依赖性凝血。
Abdominal sepsis is associated with dysfunctional hemostasis. Thrombin generation (TG) is a rate-limiting step in systemic coagulation. Neutrophils can expell neutrophil extracellular traps (NETs) and/or microparticles (MPs) although their role in pathological coagulation remains elusive. Cecal ligation and puncture (CLP)-induced TG in vivo was reflected by a reduced capacity of plasma from septic animals to generate thrombin. Depletion of neutrophils increased TG in plasma from CLP mice. Sepsis was associated with increased histone 3 citrullination in neutrophils and plasma levels of cell-free DNA and DNA-histone complexes and administration of DNAse not only eliminated NET formation but also elevated TG in sepsis. Isolated NETs increased TG and co-incubation with DNAse abolished NET-induced formation of thrombin. TG triggered by NETs was inhibited by blocking factor XII and abolished in factor XII-deficient plasma but intact in factor VII-deficient plasma. Activation of neutrophils simultaneously generated large amount of neutrophil-derived MPs, which were found to bind to NETs via histone-phosphatidylserine interactions. These findings show for the first time that NETs and MPs physically interact, and that NETs might constitute a functional assembly platform for MPs. We conclude that NET-MP complexes induce TG via the intrinsic pathway of coagulation and that neutrophil-derived MPs play a key role in NET-dependent coagulation.
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影响因子：
2.9
作者：
Kashuk, Jeffry L.;Moore, Ernest E.;Sauaia, Angela
通讯作者：
Sauaia, Angela
影响因子：
6.5
作者：
Collins, Peter W.;Macchiavello, Luis I.;Findlay, George P.
通讯作者：
Findlay, George P.
影响因子：
14.8
作者：
Lewis, Huw D.;Liddle, John;Coote, Jim E.;Atkinson, Stephen J.;Barker, Michael D.;Bax, Benjamin D.;Bicker, Kevin L.;Bingham, Ryan P.;Campbell, Matthew;Chen, Yu Hua;Chung, Chun-Wa;Craggs, Peter D.;Davis, Rob P.;Eberhard, Dirk;Joberty, Gerard;Lind, Kenneth E.;Locke, Kelly;Maller, Claire;Martinod, Kimberly;Patten, Chris;Polyakova, Oxana;Rise, Cecil E.;Ruediger, Martin;Sheppard, Robert J.;Slade, Daniel J.;Thomas, Pamela;Thorpe, Jim;Yao, Gang;Drewes, Gerard;Wagner, Denisa D.;Thompson, Paul R.;Prinjha, Rab K.;Wilson, David M.
通讯作者：
Wilson, David M.
DOI：
10.1111/j.1538-7836.2011.04544.x
发表时间：
2012-01
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Brill A;Fuchs TA;Savchenko AS;Thomas GM;Martinod K;De Meyer SF;Bhandari AA;Wagner DD
通讯作者：
Wagner DD
影响因子：
120.7
作者：
Kaukonen, Kirsi-Maija;Bailey, Michael;Bellomo, Rinaldo
通讯作者：
Bellomo, Rinaldo