Histones induce phosphatidylserine exposure and a procoagulant phenotype in human red blood cells.
Histones induce phosphatidylserine exposure and a procoagulant phenotype in human red blood cells.
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组蛋白在人红细胞中诱导磷脂酰丝氨酸的暴露和proc凝表型。
DOI：
10.1111/jth.12677
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Esmon CT
中科院分区：
文献类型：
--
作者：
Semeraro F;Ammollo CT;Esmon NL;Esmon CT
细胞外组蛋白通过刺激血细胞发挥部分血栓前活性。除了血小板，组蛋白还可以与红细胞(RBC)结合，红细胞是血栓形成的重要贡献者，但这种相互作用的功能后果知之甚少。评价组蛋白对人红细胞促凝血潜能的影响，特别是对表面磷脂酰丝氨酸(PS)表达的影响。用FITC-Annexin-V结合和流式细胞仪检测经天然组蛋白或重组单体组蛋白处理的人红细胞的PS暴露。用流式细胞仪检测钙敏感荧光载体Fluo-4 AM负载的红细胞内钙内流。用纯化的凝血酶原酶试验和一期血浆复钙凝血试验评价经组蛋白处理的红细胞的促凝血作用。天然组蛋白以剂量依赖方式诱导红细胞PS暴露，肝素或活化蛋白C分别中和或裂解组蛋白，使PS外化消失。组蛋白H4主要负责组蛋白的刺激活性，其他亚型几乎不起作用。类似地，自然组蛋白和H4诱导钙离子流入红细胞，而其他个体的组蛋白则不能。组蛋白诱导的红细胞PS的暴露转化为凝血酶原酶复合体介导的凝血酶原激活和加速血浆中纤维蛋白的形成。组蛋白通过PS的外化诱导红细胞表达促凝血剂表型。这一发现为细胞外组蛋白的血栓前活性提供了新的见解。
Extracellular histones exert part of their prothrombotic activity through the stimulation of blood cells. Besides platelets, histones can bind to red blood cells (RBCs), which are important contributors to thrombogenesis, but little is known about the functional consequences of this interaction. To evaluate the effect of histones on the procoagulant potential of human RBCs with particular regard to the expression of surface phosphatidylserine (PS). PS exposure on human RBCs treated with a natural mixture of histones or recombinant individual histones was evaluated by FITC-Annexin-V binding and measured by flow cytometry. Calcium influx in RBCs loaded with the calcium-sensitive fluorophore Fluo-4 AM was assessed by flow cytometry. The procoagulant potential of histone-treated RBCs was evaluated by a purified prothrombinase assay and a one-stage plasma recalcification clotting test. Natural histones induced PS exposure on RBCs in a dose-dependent manner and neutralization or cleavage of histones by heparin or activated protein C, respectively, abolished PS externalization. Histone H4 was mainly responsible for the stimulating activity of histones, while the other subtypes were almost ineffective. Similarly, natural histones and H4 induced influx of calcium into RBCs while the other individual histones did not. Histone-induced exposure of PS on RBCs translated into increased prothrombinase complex-mediated prothrombin activation and accelerated fibrin formation in plasma. Histones induce RBCs to express a procoagulant phenotype through the externalization of PS. This finding provides new insight into the prothrombotic activity of extracellular histones.
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细胞外组蛋白是败血症死亡的主要介体。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4
作者：
Woon, LA;Holland, JW;Roufogalis, BD
通讯作者：
Roufogalis, BD
影响因子：
20.3
作者：
Whelihan, Matthew F.;Zachary, Vicentios;Mann, Kenneth G.
通讯作者：
Mann, Kenneth G.
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：
5.6
作者：
Rosenbluh, J;Hariton-Gazal, E;Loyter, A
通讯作者：
Loyter, A