The procoagulant activity of tissue factor expressed on fibroblasts is increased by tissue factor-negative extracellular vesicles.
The procoagulant activity of tissue factor expressed on fibroblasts is increased by tissue factor-negative extracellular vesicles.
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DOI：
10.1371/journal.pone.0240189
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Collins PW
中科院分区：
文献类型：
--
作者：
Rosas M;Slatter DA;Obaji SG;Webber JP;Alvarez-Jarreta J;Thomas CP;Aldrovandi M;Tyrrell VJ;Jenkins PV;O'Donnell VB;Collins PW
组织因子（TF）对于激活血液凝固至关重要。TF功能受表达TF的细胞表面上的外化磷脂酰丝氨酸（PS）和磷脂酰乙醇胺（PE）的量调节。我们研究了PS和PE在成纤维细胞TF功能中的作用。成纤维细胞表达6-9 X IO 4个TF分子/细胞，但对于FXa生成具有低比活性。我们证实，这是与最小的外部PS和PE，并首次表征的PS/PE的分子种类表明，这些不同的血小板中发现的。用于模拟血管损伤的成纤维细胞的机械损伤增加了外化PS/PE，并导致FXa生成增加7倍，其被膜联蛋白V和抗TF抗体抑制。不表达TF的血小板衍生的细胞外囊泡（EV）支持最小的FVIIa依赖性FXa产生，但显著增加成纤维细胞TF活性。这种成纤维细胞TF活性的增强也可以使用包含10%PS而不含TF的合成脂质体来实现。总之，尽管高水平的表面TF表达，健康的成纤维细胞表达低水平的面向外部的PS和PE，限制了它们产生FXa的能力。添加血小板衍生的TF阴性EV或人工脂质体以PS依赖性方式增强成纤维细胞TF活性。这些研究结果有助于信息的机制，控制TF功能的成纤维细胞膜。
Tissue factor (TF) is critical for the activation of blood coagulation. TF function is regulated by the amount of externalised phosphatidylserine (PS) and phosphatidylethanolamine (PE) on the surface of the cell in which it is expressed. We investigated the role PS and PE in fibroblast TF function. Fibroblasts expressed 6–9 x 104 TF molecules/cell but had low specific activity for FXa generation. We confirmed that this was associated with minimal externalized PS and PE and characterised for the first time the molecular species of PS/PE demonstrating that these differed from those found in platelets. Mechanical damage of fibroblasts, used to simulate vascular injury, increased externalized PS/PE and led to a 7-fold increase in FXa generation that was inhibited by annexin V and an anti-TF antibody. Platelet-derived extracellular vesicles (EVs), that did not express TF, supported minimal FVIIa-dependent FXa generation but substantially increased fibroblast TF activity. This enhancement in fibroblast TF activity could also be achieved using synthetic liposomes comprising 10% PS without TF. In conclusion, despite high levels of surface TF expression, healthy fibroblasts express low levels of external-facing PS and PE limiting their ability to generate FXa. Addition of platelet-derived TF-negative EVs or artificial liposomes enhanced fibroblast TF activity in a PS dependent manner. These findings contribute information about the mechanisms that control TF function in the fibroblast membrane.
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影响因子：
7.1
作者：
Iba T;Ogura H
通讯作者：
Ogura H
DOI：
10.1111/j.1538-7836.2010.03826.x
发表时间：
2010-05
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Ohkubo YZ;Morrissey JH;Tajkhorshid E
通讯作者：
Tajkhorshid E
影响因子：
5.7
作者：
Gajsiewicz JM;Morrissey JH
通讯作者：
Morrissey JH
影响因子：
7.5
作者：
Morrissey JH;Davis-Harrison RL;Tavoosi N;Ke K;Pureza V;Boettcher JM;Clay MC;Rienstra CM;Ohkubo YZ;Pogorelov TV;Tajkhorshid E
通讯作者：
Tajkhorshid E
影响因子：
7.5
作者：
Ansari, Shabbir A.;Pendurthi, Usha R.;Rao, L. Vijaya Mohan
通讯作者：
Rao, L. Vijaya Mohan