项目名称: 玻璃酸两性离子化的免疫效应及其机制研究
项目编号: No.31270860
项目类型: 面上项目
立项/批准年度: 2013
项目学科: 生物科学
项目作者: 段金友
作者单位: 西北农林科技大学
项目金额: 70万元
中文摘要: 去乙酰化等结构修饰是生命体调控内源性生物大分子功能的重要手段。糖胺聚糖类大分子玻璃酸是体内重要的炎症和免疫调节因子,在N-去乙酰化酶作用下会生成玻璃酸两性离子衍生物。然而,这一生理过程的免疫效应及其机制有待研究。申请人前期研究显示,与玻璃酸不同,玻璃酸两性离子衍生物与外源性两性离子多糖具有类似的螺旋结构,暗示后两者可能以相似的信号机制诱导天然和获得性免疫。本申请拟进一步制备出不同分子量和去乙酰化度的内源性玻璃酸两性离子衍生物,从细胞和动物水平来剖析这些衍生物对抗原呈递细胞活化和初始T细胞增殖与分化的影响,考察Toll样受体、MHCⅡ类分子抗原呈递、T细胞受体交联等信号途径在上述免疫响应中的介导作用,并在分子水平上阐明构效关系。本申请对揭示玻璃酸体内两性离子化修饰所产生的免疫效应具有重要的意义,同时拓宽了两性离子多糖生物学的研究范畴,也有助于发现具有诱导调节性T细胞功能的新两性离子多糖分子。
中文关键词: 糖胺聚糖;N-去乙酰化;生物活性;透明质酸;生物大分子
英文摘要: The structural modification of endogenerous biomacromolecules including deacetylation is an important means of regulating their function. Hyaluronan,one glycosaminoglycan,is an important regulator in inflammation and immunity in vivo. The deacetylation of hyaluronan will generate the zwitterionic derivatives. However,the immunological effects and the underlying mechanisms of this physiological process remains unexplored. Previous evidence shows that different from hyaluronan,zwitterionic derivative of hyaluronan possesses a helix structure similar to that of exogenerous zwitterionic polysaccharide. This result implies that the latter two polysaccharides probably share similar mechanisms in inducing natural and adaptive immune responses. In this proposal, zwittionic derivatives of hyaluronan varied in molecular size and N-deacetylation degree will be prepared. The immune response in vitro and in vivo to these derivatives,such as the activation of antigen presenting cells as well as the proliferation and differentiation of na?ve T cells, is investigated.The role of signalings through Toll-like receptors, Major histocompatibility complexⅡ(MHC Ⅱ)antigen presentation pathway and T-cell receptor crossing will be examined. Finally,the structure-activity relationship will be discussed.This proposal provides an insight t
英文关键词: glycosaminoglycan;N-acetylation;biological activity;hyaluronic acid;biomacromolecule