GLYCOSPHINGOLIPIDS OF HUMAN ENDOTHELIAL CELLS

内皮细胞的许多特化特性是一种 特定受体和酶的功能，存在于 他们的表面。 内皮细胞被多种 刺激引起细胞表面表达的显著变化 分子及其功能特性。 醋脂 （GSL）是作为受体的细胞表面分子， 免疫原 一些血型与肿瘤相关 抗原是糖脂，以及几种糖脂的自身抗体 最近被确认。 虽然内皮细胞具有 一直是密集的生物化学研究的主题，之前， 我们的工作没有关于这些GSL的信息 细胞 我们最近确定了主要的中性GSL， 人脐静脉内皮细胞的神经节苷脂。 长 我们工作的长期目标是确定 对内皮细胞GSL的免疫攻击在 血管损伤的发病机制，以及这些GSL是否是细胞 调节分子或细胞的表面受体。 具体 这项建议的目的是确定组成方面的变化， 淋巴因子激活的GSL的细胞表面表达 内皮细胞;以确定细胞表面GSL是否介导 细胞或粘附蛋白与活化的内皮细胞的结合; 并分析人血清中自身抗体的存在 抗内皮细胞GSL抗原。 这些研究将提供 关于一类重要内皮细胞的新信息 表面分子，并将评估GSL作为受体的作用 免疫细胞和自身抗体是导致血管 损伤和动脉粥样硬化。

Many of the specialized properties of endothelial cells are a function of specific receptors and enzymes that are present on their surface. Activation of endothelial cells by a variety of stimuli causes striking changes in their expression of cell surface molecules and in their functional properties. Glycosphingolipids (GSLs) are cell surface molecules that are receptors and immunogens. A number of blood group and tumor-associated antigens are glycolipids, and autoantibodies to several glycolipids have been identified recently. Although endothelial cells have been the subject of intensive biochemical investigation, prior to our work no information was available about the GSLs of these cells. We have recently identified the major neutral GSLs and gangliosides of human umbilical vein endothelial cells. The long term objectives of our work are to determine whether an immunological attack on endothelial cell GSLs plays a role in the pathogenesis of vascular damage, and whether these GSLs are cell surface receptors for regulatory molecules or cells. The specific aims of this proposal are to identify changes in the composition and cell surface expression of GSLs of lymphokine-activated endothelial cells; to determine if cell surface GSLs mediate binding of cells or adhesion proteins to activated endothelial cells; and to analyze human sera for the presence of autoantibodies against endothelial cell GSL antigens. These studies will provide new information about an important class of endothelial cell surface molecules, and will evaluate the role of GSLs as receptors for immune cells and autoantibodies as a cause of vascular damage and atherosclerosis.