Thrombin induces platelet adhesion to endothelial cells.
Thrombin induces platelet adhesion to endothelial cells.
复制标题
凝血酶诱导血小板粘附至内皮细胞。
DOI：
10.1055/s-2007-1002435
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发表时间：
1992
影响因子：
5.7
通讯作者：
Kaplan,JE
中科院分区：
文献类型：
--
作者：
Venturini,CM;Kaplan,JE
止血需要密切调节血管壁、血小板和可溶性凝血因子之间的相互作用。内皮细胞的非血栓形成性质对于通过维持血管通畅来控制血流是必不可少的。然而，为了保存血容量，止血必须快速有效。血小板容易粘附于内皮细胞外基质。如果血管被切断，或者由于损伤而失去内皮衬里，血小板粘附到暴露的基质上并引发血栓的形成。这是一个经过充分研究的现象（综述见Turitto和Baumgartner 1以及Sixma等人2）。内皮细胞的非血栓形成性质可能受到损害。在暴露于改变的流动条件、3无脱离的损伤、4暴露于氧自由基、5化疗、6肿瘤细胞粘附、7和暴露于某些促凝剂（特别是凝血酶）后，观察到血小板粘附于血管。8凝血酶改变内皮细胞和血小板形态。8凝血酶诱导血小板粘附于汇合的内皮细胞单层。[9]向孵育混合物中加入肝素可逆转这种粘附。10我们已经开发了两种实验模型，促进了凝血酶诱导的血小板粘附的研究。在血小板粘附的体外模型中，将培养的绵羊肺动脉内皮细胞的11个汇合单层与分离的放射性标记的绵羊血小板一起孵育。之后，洗涤单层，并使用放射性同位素计数评估粘附血小板的数量。很少有血小板粘附在未处理的内皮细胞单层上。向孵育混合物中添加凝血酶显著增强血小板粘附。大多数血小板以聚集体形式粘附。此外，凝血酶预处理的内皮细胞支持更多的血小板粘附比未经处理的单层，去除流体相凝血酶后。在该模型中，如扫描电子显微镜所示，血小板-内皮相互作用如图1所示。在凝血酶诱导的血小板粘附的第二个模型中，用缓冲液离体灌注离体大鼠肺并进行呼吸。很少有血小板粘附在未经治疗的肺上。[12]在凝血酶循环和从肺中冲洗出液相凝血酶后，发生了显著更多的血小板粘附。这种独特的模型检查了流动条件下单个血小板与完整血管系统的粘附。在这些条件下粘附于肺血管的血小板如图2所示。本文的目的是审查调查进行了自己和他人之间的相互作用凝血酶，血小板和内皮细胞。重点放在凝血酶诱导血小板粘附直接内皮细胞。将检查内皮介质，其改变血小板反应性，从而改变对内皮的粘附。此外，我们将描述我们目前的研究血小板内皮细胞的相互作用。
Hemostasis requires close regulation of the interactions between the vessel wall, platelets, and soluble coagulation factors. The nonthrombogenic nature of the endothelial cell is essential to the control of blood flow by acting to maintain vascular patency. However, in order to conserve blood volume, hemostasis must be rapid and effective. Platelets readily adhere to endothelial extracellular matrix. If a vessel is severed, or the endothelial lining lost due to injury, platelets adhere to exposed matrix and initiate the formation of a thrombus. This is a well-studied phenomenon (for review see Turitto and Baumgartner1 and Sixma et al2). The nonthrombogenic nature of the endothelial cell can be compromised. Platelet adhesion to vessels is seen after exposure to altered flow conditions, 3 injury without detachment, 4 exposure to oxygen free radicals, 5 chemotherapy, 6 tumor cell adhesion, 7 and exposure to certain procoagulants, specifically thrombin. 8 Thrombin alters both endothelial cell and platelet morphology. 8 Thrombin induces platelet adhesion to confluent endothelial cell monolayers. 9 This adhesion is reversed by addition of heparin to the incubation mixture. 10 We have developed two experimental models that have facilitated the study of thrombin-induced platelet adhesion. In an in vitro model of platelet adhesion, 11 confluent monolayers of cultured sheep pulmonary artery endothelial cells are incubated with isolated radiolabeled sheep platelets. Afterward, the monolayers are washed and the number of adherent platelet assessed using radioisotope counting. Few platelets adhere to untreated endothelial cell monolayers. The addition of thrombin to the incubation mixture significantly enhances platelet adhesion. Most platelets are adherent as aggregates. Furthermore, thrombin pretreated endothelial cells support more platelet adhesion than untreated monolayers, after the removal of fluid-phase thrombin. In this model, platelet-endothelial interactions, as depicted by scanning electron microscopy, are shown in Figure 1. In a second model of thrombin-induced platelet adhesion, isolated rat lungs are perfused ex vivo with buffer and respirated. Few platelets adhere to untreated lungs. 12 After circulation of thrombin and washout of the fluidphase thrombin from the lung, significantly more platelet adhesion occurs. This unique model examines single platelet adhesion to an intact vasculature under flow conditions. Platelets adherent to the pulmonary vasculature under these conditions are shown in Figure 2. The goal of this article is to review investigations conducted by ourselves and others on the interactions among thrombin, platelets, and endothelial cells. Emphasis is placed on thrombin induction of platelet adhesion directly to endothelial cells. The endothelial mediators, which modify platelet reactivity, and thus adhesion to endothelium, will be examined. In addition, we will describe our current studies of the platelet-endothelial interaction.