Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis
Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis
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DOI：
10.3324/haematol.2012.066167
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发表时间：
2012-12-01
期刊：
影响因子：
--
通讯作者：
Dignat-George, Francoise
中科院分区：
文献类型：
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作者：
Lacroix, Romaric;Plawinski, Laurent;Dignat-George, Francoise
背景我们最近在体外将一种新的纤溶功能赋予了细胞来源的微粒。在这项研究中，我们探讨了这种新的属性的微粒在vivo situation.Design和MethodsCirculating微粒的相关性，从血栓性血小板减少性紫癜或心血管疾病患者的血浆和健康受试者分离。微粒也从纯化的人血细胞亚群中获得。微粒上的纤溶酶原激活剂进行了鉴定，通过流式细胞术和酶联免疫吸附试验，他们产生纤溶酶的能力进行了定量与显色试验和他们的纤溶活性测定zymography.ResultsCirculating从患者分离的微粒产生一系列的纤溶酶活性在其表面。这一特性与尿激酶型纤溶酶原激活物和/或组织纤溶酶原激活物的含量可变有关。使用不同的微粒亚群，我们证明，纤溶酶是产生内皮细胞和白细胞微粒，但不是血小板或红细胞来源的微粒。白细胞衍生的微粒承担尿激酶型纤溶酶原激活剂及其受体，而内皮微粒携带组织纤溶酶原激活剂和组织纤溶酶原激活剂/抑制剂complex.ConclusionsEndothelial和白细胞微粒，分别携带组织纤溶酶原激活剂或尿激酶型纤溶酶原激活剂，支持在病理环境中调制的循环中的纤溶活性的一部分。认识到这种由微粒传递的血液传播的纤维蛋白溶解活性提供了对微粒在止血平衡中的作用的更全面的看法。
BackgroundWe recently assigned a new fibrinolytic function to cell-derived microparticles in vitro. In this study we explored the relevance of this novel property of microparticles to the in vivo situation.Design and MethodsCirculating microparticles were isolated from the plasma of patients with thrombotic thrombocytopenic purpura or cardiovascular disease and from healthy subjects. Microparticles were also obtained from purified human blood cell subpopulations. The plasminogen activators on microparticles were identified by flow cytometry and enzyme-linked immunosorbent assays; their capacity to generate plasmin was quantified with a chromogenic assay and their fibrinolytic activity was determined by zymography.ResultsCirculating microparticles isolated from patients generate a range of plasmin activity at their surface. This property was related to a variable content of urokinase-type plasminogen activator and/or tissue plasminogen activator. Using distinct microparticle subpopulations, we demonstrated that plasmin is generated on endothelial and leukocyte microparticles, but not on microparticles of platelet or erythrocyte origin. Leukocyte-derived microparticles bear urokinase-type plasminogen activator and its receptor whereas endothelial microparticles carry tissue plasminogen activator and tissue plasminogen activator/inhibitor complexes.ConclusionsEndothelial and leukocyte microparticles, bearing respectively tissue plasminogen activator or urokinase-type plasminogen activator, support a part of the fibrinolytic activity in the circulation which is modulated in pathological settings. Awareness of this blood-borne fibrinolytic activity conveyed by microparticles provides a more comprehensive view of the role of microparticles in the hemostatic equilibrium.