Regulation of Leukocyte Adhesion Receptor Function

白细胞粘附受体功能的调节

• 批准号: 9017743
• 负责人: Eric Martz
• 金额: $ 27.66万
• 依托单位: University of Massachusetts Amherst
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1996-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9017743&HistoricalAwards=false
• 关键词: Regulation; Leukocyte; Adhesion; Receptor; Function

The leukocyte adhesion molecule LFA-1 plays a crucial role in all forms and levels of immunity. Leukocytes are able to turn LFA-1 function on or off on a minute-by-minute basis, giving them precise control over their adhesions with each other and other cells. The rapid regulation of LFA-1 function is mediated by protein kinase C, and does not require changes in cell surface density of LFA-1 or its ligand, ICAM-1. Rather, the regulation of the avidity of LFA-1 for ICAM-1 involves poorly defined configurational changes. Elucidation of these configurational changes is the goal of this research. Highly plausible changes would be homotypic clustering of LFA-1 to increase avidity for ICAM-1 and anchoring to the cytoskeleton. The approach proposed is to quantitate clustering by flow cytometric analysis of fluorescence resonance energy transfer, a method proven capable of estimating mean intermolecular distances on cell surfaces. The ability to quantitate clustering will make it possible to explore its mechanisms, including the roles of divalent cations and cytoskeleton. Anchoring to the cytoskeleton will be evaluated by solubility in Triton X-100. Cellular adhesion plays a critical role in many developmental and physiological processes, including immune function. The molecular mechanisms by which cells recognize and adhere to appropriate partners is a subject of great current interest. The proposed research will explore an innovative approach to the study of mechanisms by which the strength of adhesion between cells is regulated.

白细胞粘附分子LFA-1在所有的 免疫力的形式和水平。 白细胞能够将LFA-1 以分钟为单位开启或关闭， 控制它们与彼此和其他细胞的粘附。 的 蛋白激酶介导LFA-1功能的快速调节 C，并且不需要改变LFA-1的细胞表面密度 或其配体ICAM-1。 相反，调节的贪婪， ICAM-1的LFA-1涉及不明确的构型变化。 阐明这些配置变化是本文的目标 research. 高度合理的变化将是同型聚类 LFA-1增加对ICAM-1的亲合力，并锚定到 细胞骨架 提出的方法是量化聚类 通过荧光共振能量的流式细胞术分析 转移，证明能够估计平均分子间 细胞表面的距离。 量化聚类的能力 将有可能探讨其机制，包括 二价阳离子和细胞骨架的作用。 锚固到 通过在Triton X-100中的溶解度评价细胞骨架。 细胞粘附在许多发育和生长过程中起着关键作用， 生理过程，包括免疫功能。 分子 细胞识别和粘附合适的细胞的机制 伙伴关系是当前人们非常感兴趣的一个主题。 拟议 研究将探索一种创新的方法来研究 细胞间粘附强度的机制是 监管.