SHEDDING, SECRETION, & TRANSFER OF GLYCOSPHINGOLIPIDS

鞘糖脂是细胞膜的重要组成部分。 低聚糖结构的巨大多样性和 合成这些物质所需的糖基转移酶的数量 结构表明，它们可能具有重要的功能。AS 例如，它们确实起到了人类血型同种异体的作用 自身抗原，作为病毒和毒素的受体，如肿瘤 标记物，并参与细胞与细胞的相互作用。其中一些 功能，如毒素结合和抗原性，已经被 被动地转移到细胞中，使细胞与 适当的神经鞘糖脂。许多与肿瘤相关的 已经描述了鞘糖脂，其中一些已经脱落 通过肿瘤细胞。因为一些鞘糖脂抑制了 体外免疫反应性，鞘糖脂从 肿瘤可能是免疫抑制的原因之一 各种形式的人类癌症。 鞘糖脂在水中形成胶束，因为单体是 几乎是无法溶解的。相当集中的 糖鞘糖脂是在血浆中发现的，它们只有 与脂蛋白有关。人们对此知之甚少 鞘糖脂进入血浆的机制，无论是通过 分泌物，从膜上脱落或从细胞吸收 通过脂蛋白形成细胞膜。 这项建议的最终目标是理解 鞘糖脂分泌或排出的机制 正常和恶性细胞，与血浆脂蛋白相互作用， 脂蛋白之间的转移，以及从脂蛋白转移到 或进入其他细胞。将以人类肿瘤细胞系为模型 目的：研究神经鞘糖脂的分泌或脱落情况。 脂蛋白在这一过程中的作用。来自不同个人的血液 对于不同的鞘糖脂血型抗原将被使用 研究黄曲霉毒素转移的动力学和机理 血浆脂蛋白之间和血浆脂蛋白之间的鞘糖脂 脂蛋白和人类红细胞、淋巴细胞和血小板。 这项工作将使我们更好地理解 外源性鞘糖脂对细胞功能和细胞表面的影响 地形。它还将提供更深入的洞察，了解 脂蛋白相互作用，并与细胞相互作用。

Glycosphingolipids are important constituents of cell membranes. The tremendous diversity of oligosaccharide structure and the number of glycosyltransferases necessary for synthesizing these structures suggest that they may have significant functions. As examples, they do function as human blood group allo- and autoantigens, as receptors for viruses and toxins, as tumor markers, and are involved in cell-cell interactions. Some of these functions, such as toxin binding and antigenicity, have been passively transferred to cells incubating the cells with the appropriate glycosphingolipid. Many tumor-associated glycosphingolipids have been described and some of these are shed by the tumor cells. Since some glycosphingolipids suppress immune responsiveness in vitro, glycosphingolipids shed from tumors may contribute to the immunosuppression found with some forms of human cancer. Glycosphingolipids form micelles in water since the monomers are virtually insoluble. Significant concentrations of glycosphingolipids are found in plasma and they are exclusively associated with lipoproteins. Little is known about the mechanisms by which glycosphingolipids enter plasma, whether by secretion, shedding from membranes, or absorption from cell membranes by lipoproteins. The ultimate goal of this proposal is to understand the mechanisms by which glycosphingolipids are secreted or shed from normal and malignant cells, interact with plasma lipoproteins, transfer between lipoproteins, and transfer from lipoproteins onto or into other cells. Human tumor cell lines will be used as models to study the secretion or shedding of glycosphingolipids and the role of lipoproteins in this process. Blood from various individuals with differing glycosphingolipid blood group antigens will be used to study the kinetics and mechanisms of transfer of glycosphingolipids between plasma lipoproteins and between lipoproteins and human erythrocytes, lymphocytes, and platelets. This work will lead to a better understanding of the way exogenous glycosphingolipids affect cell function and cell surface topography. It will also provide deeper insight into how lipoproteins interact with each other and with cells.