VASCULAR RECEPTORS FOR PLATELET-DERIVED GROWTH FACTOR

血小板在血管损伤部位的聚集导致血管释放 一种刺激血管平滑肌生长的血小板蛋白 细胞，并引发各种代谢反应。这种蛋白质， 血小板衍生生长因子(PDGF)被认为在 动脉粥样硬化的增生性血管病变。它还刺激了 血管平滑肌细胞释放前列环素。我们有 最近发现，除了对平滑肌细胞的作用外，PDGF 是一种对人多形核白细胞非常有效的化学诱导剂。 推测这种趋化作用在炎症反应中很重要。 血管损伤部位的血小板引起的反应。我们的目标是 探讨PDGF作用的第一步。具体来说，我们 将研究PDGF与其在血管上的受体位置的相互作用 平滑的肌肉细胞。对于这些研究，我们将对PDGF进行放射性标记 并将使用放射性配基结合技术来识别受体 网站。我们将记录结合部位是否具有适当的 PDGF受体的亲和力、特异性和动力学预期。我们会 然后用这些方法来研究pdgf受体的调节。 各种调制影响，包括细胞密度的变化， 长期接触PDGF，并用5-羟色胺(一种增强剂)进行预治疗 PDGF活性的变化。使用PDGF偶联铁蛋白，我们将对PDGF进行本地化 通过电子显微镜观察受体，并将研究PDGF 人类白细胞上的受体将使我们能够研究这种可能性 在疾病状态下存在着PDGF受体的全身性变化 例如动脉粥样硬化，其中可能存在异常的增殖物 对PDGF的反应。这些研究应该为深入了解这种机制提供帮助。 PDGF作为促有丝分裂和炎症介质的作用，应该增强 我们不了解血小板产品对血管的影响。

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.