VASCULAR RECEPTORS FOR PLATELET-DERIVED GROWTH FACTOR

血小板在血管损伤部位的聚集导致 一种刺激血管平滑肌生长的血小板蛋白质 细胞并激发各种代谢反应。 这种蛋白质， 血小板衍生生长因子（PDGF），被认为在 动脉粥样硬化的增殖性血管病变。 它还刺激了 前列环素从血管平滑肌细胞释放。我们有 最近发现，除了对平滑肌细胞的作用外，PDGF 是一种对人类多形核白细胞非常有效的化学引诱物。 据推测，这种趋化作用在炎症反应中是重要的。 血小板在血管损伤部位引起的反应。 我们的目标是 研究PDGF作用的第一步。 我们特别 将研究PDGF与其在血管上的受体位点的相互作用， 平滑肌细胞 对于这些研究，我们将放射性标记PDGF 并将使用放射性配体结合技术来识别受体 网站. 我们将记录结合位点具有适当的 预期的PDGF受体的亲和力、特异性和动力学。 我们将 然后用这些方法研究PDGF受体的调节， 多种调节影响，包括细胞密度的改变， 长期暴露于PDGF，并用5-羟色胺（一种增效剂）预处理 PDGF活性。 使用PDGF与铁蛋白偶联，我们将定位PDGF 受体，并将研究PDGF是否 人类白细胞上的受体将使我们能够研究 疾病状态下PDGF受体的普遍改变 例如动脉粥样硬化，其中可能存在异常增殖性 对PDGF的反应这些研究应该提供深入了解的机制， PDGF作为促有丝分裂剂和炎症剂的作用， 我们对血小板制品对血管影响的了解。

The aggregation of platelets at sites of vascular injury causes release of a platelet protein which stimulates the growth of vascular smooth muscle cells and elicits a variety of metabolic responses. This protein, platelet-derived growth factor (PDGF), is thought to play a role in the proliferative vascular lesions of atherosclerosis. It also stimulates the release of prostacycline from vascular smooth muscle cells. We have recently found that in addition to its effects on smooth muscle cells, PDGF is a very potent chemoattractant for human polymorphonuclear leukocytes. Presumably this chemotactic effect is important in the inflammatory response elicited by platelets at the site of vascular damage. Our goal is to investigate the first steps in the action of PDGF. Specifically, we will study the interaction of PDGF with its receptor sites on vascular smooth muscle cells. For these studies we will radioactively label PDGF and will use radioligand binding techniques to identify the receptor sites. We will document that the binding sites have the appropriate affinity, specificity, and kinetics expected of PDGF receptors. We will then use these methods to study the regulation of PDGF receptors by a variety of modulatory influences including alterations in cell density, chronic exposure to PDGF, and pre-treatment with serotonin, a potentiator of PDGF activity. Using PDGF coupled to ferritin, we will localize PDGF receptors by electron microscopy and will investigate whether PDGF receptors on human leukocytes will allow us to investigate the possibility that there are generalized alterations of PDGF receptors in disease states such as atherosclerosis in which there may be an abnormal proliferative response to PDGF. These studies should provide insight into the mechanism of action of PDGF as a mitogenic and inflammatory agent and should enhance our undrestanding of the effects of platelet products on blood vessels.