PLATELET-ENDOTHELIAL CELL INTERACTIONS
血小板-内皮细胞相互作用
基本信息
- 批准号:3344691
- 负责人:
- 金额:$ 13.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1989
- 资助国家:美国
- 起止时间:1989-07-01 至 1992-06-30
- 项目状态:已结题
- 来源:
- 关键词:anticoagulants blood coagulation tests blood viscosity cardiovascular disorder chemotherapy cardiovascular pharmacology cell adhesion cell cell interaction coagulation factor VIII eicosanoid metabolism fluorescence microscopy granulocyte human subject immunofluorescence technique leukocytes phantom model platelet aggregation prostacyclins prostaglandin E prostaglandin inhibitors radioimmunoassay thrombosis tissue /cell culture vascular endothelium vasculitis video recording system
项目摘要
Clinical experience over the last two decades has shown that
antiplatelet--therapy is often not effective in the treatment of
arterial thrombotic disorders. Patients on aspirin and other
agents which impair platelet cyclooxygenase and the platelet
release reaction continue to suffer recurrent episodes of
myocardial ischemia or recurrent stroke. We therefore hypothesize
that some arterial thrombotic disorders are in part due to the
procoagulant activity (PCA) of a stimulated, inflammed or injured
vessel wall. This view is in keeping with recent in vitro data
that vascular endothelium, when stimulated by inflammatory/immune
mediators such as interleukin-l (IL-l), tissue necrosis factor
(TNF), lymphotoxin or hepatic stimulating factor, can become
prothrombotic by generating, for example, tissue factor and
molecules adhesive for granulocytes. Simultaneously, vasculitis
and/or vessel wall injury may diminish the production of substances
of arachidonate (prostacyclin and PGE2) and non-arachidonate
(endothelial cell relaxing factor) metabolism which normally
modulate leukocyte-platelet adhesion/aggregation. The experimental
approach taken here to evaluate this hypothesis is to simulate in
vitro flow through a microvessel. We do so by utilizing a flow
chamber which incorporates whole blood, arterial-like shear rates,
a flow path of thickness 290 um, and in situ epifluorescence video-
microscopy of leukocyte-platelet adhesion/aggregation to a defined
injury site on an endothelial cell monolayer. Our aims include 1)
establishing the effects of flow (shear rate and shear stress) on
PCA; 2) determining the dependence on flow of granulocyte adhesion
to non-injured endothelium; and 3) determining the flow dependence
of leukocyte-platelet adhesion/aggregation to a site of defined
injury to endothelium. PCA will be measured with flowing, cell-
free media and a radiometric assay for Factor Xa conversion. For
imaging purposes,platelets will be labelled with a fluorescein-
conjugated monoclonal antibody (TAB) to glycoprotein IIB, while
monocyte-granulocytes will be labelled with a rhodamine-conjugated
monoclonal antibody directed against the Mo5 antigen. In
particular, we seek a rational basis for the use of anticoagulant
therapy in certain cases of arterial thrombosis.
过去二十年的临床经验表明,
抗血小板治疗在治疗
动脉血栓性疾病 服用阿司匹林和其他药物的患者
损害血小板环氧合酶和血小板的药剂
释放反应继续反复发作,
心肌缺血或复发性中风。 因此我们假设
一些动脉血栓性疾病部分是由于
促凝血活性(PCA)的刺激,炎症或损伤
血管壁 这一观点与最近的体外数据一致
当血管内皮受到炎症/免疫刺激时,
介质如白细胞介素-I(IL-1)、组织坏死因子
(TNF),光敏素或肝刺激因子,可以成为
通过产生例如组织因子和
粘附粒细胞的分子。 同时,血管炎
和/或血管壁损伤可减少物质的产生
花生四烯酸(前列环素和PGE 2)和非花生四烯酸
(内皮细胞松弛因子)代谢,
调节白细胞-血小板粘附/聚集。 实验
在此采用的评估该假设的方法是模拟
通过微血管的体外流动。 我们利用一种流动
腔室,其包含全血、动脉样剪切率,
厚度为290 μ m的流动路径,以及原位荧光视频-
白细胞-血小板粘附/聚集的显微镜检查
内皮细胞单层上损伤部位。 我们的目标包括:1)
确定流动(剪切速率和剪切应力)对
PCA; 2)确定粒细胞粘附对流量的依赖性
至未损伤的内皮;以及3)确定流量依赖性
白细胞-血小板粘附/聚集到确定的
内皮损伤。 PCA将通过流动的细胞进行测量-
游离培养基和Xa因子转化的放射性测定。 为
为了成像,血小板将用荧光素标记,
与糖蛋白IIB偶联的单克隆抗体(TAB),而
单核细胞-粒细胞将用罗丹明缀合的
抗Mo 5单克隆抗体。 在
特别是,我们寻求抗凝剂使用的合理依据
治疗某些动脉血栓形成的病例。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Eric Franklin Grabowski其他文献
Eric Franklin Grabowski的其他文献
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{{ truncateString('Eric Franklin Grabowski', 18)}}的其他基金
The Roles of Complement Activation vs. Shiga Toxin Binding to Endothelium in eHUS.
eHUS 中补体激活与志贺毒素与内皮细胞结合的作用。
- 批准号:
10078268 - 财政年份:2019
- 资助金额:
$ 13.15万 - 项目类别:
The Roles of Complement Activation vs. Shiga Toxin Binding to Endothelium in eHUS.
eHUS 中补体激活与志贺毒素与内皮细胞结合的作用。
- 批准号:
10323266 - 财政年份:2019
- 资助金额:
$ 13.15万 - 项目类别:
Tissue Factor, Flow, and Platelet Adhesion/Aggregation on Activated Endothelium
活化内皮上的组织因子、血流和血小板粘附/聚集
- 批准号:
8049138 - 财政年份:2008
- 资助金额:
$ 13.15万 - 项目类别:
Tissue Factor, Flow, and Platelet Adhesion/Aggregation on Activated Endothelium
活化内皮上的组织因子、血流和血小板粘附/聚集
- 批准号:
7465832 - 财政年份:2008
- 资助金额:
$ 13.15万 - 项目类别:
Tissue Factor, Flow, and Platelet Adhesion/Aggregation on Activated Endothelium
活化内皮上的组织因子、血流和血小板粘附/聚集
- 批准号:
7813875 - 财政年份:2008
- 资助金额:
$ 13.15万 - 项目类别:
Tissue Factor, Flow, and Platelet Adhesion/Aggregation on Activated Endothelium
活化内皮上的组织因子、血流和血小板粘附/聚集
- 批准号:
7613482 - 财政年份:2008
- 资助金额:
$ 13.15万 - 项目类别:
Induction of Tissue Factor by Patient Sera in HUS
HUS 患者血清诱导组织因子
- 批准号:
7229792 - 财政年份:2006
- 资助金额:
$ 13.15万 - 项目类别:
Induction of Tissue Factor by Patient Sera in HUS
HUS 患者血清诱导组织因子
- 批准号:
7039868 - 财政年份:2006
- 资助金额:
$ 13.15万 - 项目类别:














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