MAST CELL MEMBRANE GLYCOLIPID EXPRESSION AND FUNCTION

肥大细胞膜糖脂的表达和功能

• 批准号: 3086761
• 负责人: MICHAEL B RAIZMAN
• 金额: $ 6.18万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 1993-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3086761
• 关键词: DNA replication; bone marrow; carboxylation; cell biology; cell differentiation; cell growth regulation; chemical binding; cyclic AMP; fibroblasts; gangliosides; gene expression; histamine; hypersensitivity; interleukin 3; laboratory mouse; lipid biosynthesis; lymphokines; mast cell; membrane activity; membrane lipids; radioassay; tissue /cell culture

The overall objective of this proposal is to develop basic research skills in immunology and biochemistry through the investigation of mast cell membrane glycosphingolipids. The proposed research is designed to learn more about mast cell differentiation through studies of the expression and function of a cholera toxin-binding glycosphingolipid, ganglisoside GM1, on mouse mast cells at different stages of development. The binding of cholera toxin to ganglioside GM1 on the plasma membranes of interleukin 3- dependent, mouse bone marrow culture-derived mast cells induces an increase in both the histamine content and the DNA synthesis of these cells. The first specific aim is to quantify the surface expression and biosynthesis of ganglioside GM1 in culture-derived mast cells maintained in interleukin 3 with or without an additional proliferative signal from interleukin 4, in culture- derived mast cells further differentiated in vitro by co-culture with fibroblasts, and in peritoneal mast cells ex vivo; and to determine if the effects of cholera toxin on the histamine and cyclic adenosine monophosphate contents of these populations correlate with ganglioside GM1 expression. The second specific aim is to determine whether cholera toxin increases the histamine content of culture-derived mast cells by augmenting their histidine uptake and/or decarboxylation of histidine, and if so, to determine whether this effect correlates with ganglioside GM1 expression in the more differentiated mast cell populations. The third specific aim is to determine whether cholera toxin promotes DNA synthesis in the mast cell populations by acting as a cell cycle progression factor and whether the effect of the toxin is similar or different than that of interleukin 4. The proposed research will yield new basic information about the first glycosphingolipid-dependent functional response to be described in mast cells. These responses involve two important aspects of mast cell biology, namely, control of cellular histamine content and the regulation of mast cell replication. While these studies will focus on mouse mast cells, the knowledge and skills obtained should be directly applicable to future studies of the immunobiology and biochemistry of human mast cells, including those involved in ocular immediate hypersensitivity reactions.

这项建议的总体目标是发展基础研究 免疫学和生物化学的技能，通过调查 肥大细胞膜鞘糖脂。 拟议的研究是 旨在了解更多关于肥大细胞分化， 霍乱毒素结合蛋白的表达和功能研究 神经节苷脂GM 1对小鼠肥大细胞的作用 不同发展阶段 霍乱毒素与 神经节苷脂GM 1对白细胞介素3- 依赖性小鼠骨髓培养衍生的肥大细胞诱导 组胺含量和DNA合成都增加 这些细胞。 第一个具体目标是量化表面 神经节苷脂GM 1在培养细胞中的表达和生物合成 肥大细胞维持在白细胞介素3中， 来自白细胞介素4的额外增殖信号，在培养物中， 衍生的肥大细胞通过共培养在体外进一步分化 与成纤维细胞，和腹膜肥大细胞离体;和 确定霍乱毒素对组胺的影响， 环磷酸腺苷含量 与神经节苷脂GM 1表达相关。 第二特定 目的是确定霍乱毒素是否会增加组胺 通过增加培养来源的肥大细胞的含量， 组氨酸摄取和/或组氨酸脱羧，如果是这样， 确定这种效应是否与神经节苷脂GM 1相关 在更分化的肥大细胞群体中表达。 的 第三个具体目标是确定霍乱毒素是否促进 肥大细胞群中作为细胞的DNA合成 周期进展因子以及毒素的作用是否 与白细胞介素4相似或不同。 拟议 研究将产生新的基本信息， 鞘糖脂依赖性功能反应， 肥大细胞 这些反应涉及两个重要方面， 肥大细胞生物学，即控制细胞组胺含量 和肥大细胞复制的调节。 虽然这些研究 将重点介绍小鼠肥大细胞的知识和技能， 应直接适用于未来的研究， 人肥大细胞免疫生物学和生物化学，包括 与眼部速发型超敏反应有关。