BIOCHEMICAL PATHWAYS OF PLATELET ACTIVATION

这项研究的总体目标是描绘生物化学 在由结合引发的过程中起作用的途径 表面受体的激动剂，并导致血小板分泌， 纤维蛋白原结合位点的活化和聚集。 的一部分 我们正在进行的研究在这方面的调查，我们已经准备好了 并分离刺激性单克隆抗体（M.Ab.），名为F- 11. M.Ab. F-11作为一种激动剂，诱导分泌， 人血小板的聚集。 的临床意义 激活血小板的抗体是有据可查的，但 详细描述了作为 受体在这个过程中和生化途径触发 这种抗体还没有被描述出来。 我们预计 详细研究了M.Ab. F-11将开始填补这些空白。 的 使用M. Ab。F-11有两个明显的优点：1） M. Ab识别的蛋白质血小板表面的F-11 在我们的实验室中鉴定并部分表征。 所以我们 现在的研究集中在由受体启动的激活过程上， 其分子实体是已知的。 2)的激活 用纯化的M.Ab. F-11涉及滞后 时间为6至20分钟，这取决于M. Ab。F-11 浓度. 此延迟期允许详细 测量分子事件的序列， 血小板分泌和聚集。 因此，研究 提交的计划旨在实现以下具体目标 目的：1）纯化非变性形式的血小板 M. Ab识别的表面蛋白。F-11; 2） F-11抗原和调查是否是一种独特的 受体，受体复合物的一部分，为一个自然的- 发生血小板激动剂，或已知信号的成分 转导系统，3）测定生物化学 在F-11激活血小板中起作用的途径;以及4） 抗结核分枝杆菌多克隆和单克隆抗体的研制 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F-11抗原 我们期望， 这些研究目标将提供新的和重要的信息 血小板活化的基本机制。 的 这些研究对健康的影响尤其 与病理生理状态相关，涉及以下因素的相互作用： 抗体与循环血小板。

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.