BIOCHEMICAL PATHWAYS OF PLATELET ACTIVATION

本研究的总体目标是勾勒出生物化学。 在由结合启动的过程中运行的通路 一种表面受体的激动剂，导致血小板分泌， 纤维蛋白原结合部位的激活和聚集。作为以下内容的一部分 我们在这方面正在进行的研究，我们已经准备好 并分离到一株刺激性单抗(M.Ab)，命名为F- 11.M.Ab.F-11作为一种激动剂，诱导分泌和 人类血小板的聚集。血管紧张素转换酶的临床意义 激活血小板的抗体有很好的文献记载，但 表面抗原的详细特征 这一过程中的受体及其触发的生化途径 由这种抗体引起的疾病尚未被描述出来。我们期待着 对M.Ab.的详细研究F-11将开始填补这些空白。这个 使用M.Ab.F-11提供了两个明显的优势：1) 由M.Ab识别的蛋白质。血小板表面的F-11已经被 在我们的实验室中进行了鉴定和部分表征。因此，我们的 现在的研究集中在受体启动的激活过程上 其分子实体已为人所知。2)激活 用纯化的抗结核分枝杆菌抗体抗体制备人血小板。F-11战机出现了滞后 时间为6至20分钟，取决于M.Ab.F-11 集中精神。此延迟期允许详细 对导致分子事件序列的测量 血小板分泌和聚集。因此，这项研究 在此提交的计划旨在实现以下具体目标 目的：1)纯化一种非变性形式的血小板 M.Ab.识别的表面蛋白。F-11；2)表征 F-11抗原及其是否为独一无二的 受体，天然的-受体复合体的一部分 发生的血小板激动剂，或已知信号的成分 转导系统，3)生化测定 F-11激活血小板的途径(S)；4) 抗猪传染性支气管炎多克隆和单抗的研究进展 纯化的F-11受体，用于细胞定位、组织 分布，并用于功能结构域的免疫作图 血小板的F-11抗原。我们期待着这一成就 这些研究目标将提供新的有意义的信息 关于血小板活化过程中的基本作用机制。这个 这些研究对健康的影响尤其显著。 与涉及相互作用的病理生理状态有关 抗体与循环中的血小板有关。

The overall goal of this research is the delineation of biochemical pathways which operate in the process initiated by the binding of an agonist to surface receptors, and leading to platelet secretion, activation of fibrinogen binding sites and aggregation. As part of our ongoing studies in this line of investigation, we have prepared and isolated a stimulatory monoclonal antibody (M.Ab.), named F- 11. M.Ab. F-11 acts as an agonist which induces secretion and aggregation of human platelets. The clinical significance of antibodies which activate platelets is well documented, but detailed characterization of the surface antigens that serve as receptors in this process and the biochemical pathways triggered by such antibodies has not yet been delineated. We expect that detailed studies of M.Ab. F-11 will begin to fill these gaps. The use of M.Ab. F-11 provides two distinct advantages: 1) The protein recognized by M.Ab. F-11 on the platelet surface has been identified and partially characterized in our laboratory. Thus, our studies focus now on an activation process initiated by a receptor whose molecular entity is already known. 2) The activation of human platelets by purified IgG of M.Ab. F-11 involves a lag period of 6 to 20 minutes which is dependent on M.Ab. F-11 concentration. This latency period permits detailed measurements of the sequence of molecular events leading to platelet secretion and aggregation. Accordingly, the Research Plan submitted here is designed to achieve the following specific goals: 1) Purification of a non-denatured form of the platelet surface protein recognized by M.Ab. F-11; 2) Characterization of the F-11 antigen and investigation as to whether it is a unique receptor, part of the receptor complex for one of the naturally- occurring platelet agonists, or a component of a known signal transduction system, 3) Determination of the biochemical pathway(s) operating in the activation of platelets by F-11; and, 4) Development of polyclonal and monoclonal antibodies to the purified F-11 receptor, for use in cellular localization, tissue distribution, and for immunological mapping of functional domains of the platelet F-11 antigen. We expect that accomplishment of these research goals will provide new and significant information on basic mechanisms operating during platelet activation. The health-related implications of these studies are particularly relevant to pathophysiological states involving interaction of antibodies with circulating platelets.