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Analysis of the mechanism of regulation of lipid rafts within the lymphocyte plasma membrane by the lamellar-shaped nanodomain-structured surface

层状纳米结构表面调节淋巴细胞质膜内脂筏的机制分析

基本信息

批准号：
15500329
负责人：
ABE Kazuhiko
金额：
$ 1.28万
依托单位：
Tokyo Women's Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Recently, the presence of lipid rafts allowing efficient signal transduction within the plasma membrane of the cell was proposed by Simons K and Ikonen E. It was reported that a decrease in the cholesterol content of lipid rafts by treatment with methyl-β-cyclodextrin(MβCD) disturbed signal transduction, and that selective removal of carbohydrates from the glycosphingolipid of lipid rafts by treatment with endoglycoceramidase II plus activator II(EGPA) impaired activation of the Src family of tyrosine kinases through crosslinking of glycosylphosphatidylinositol(GPI)-anchored proteins. Based on these findings, this study was conducted to determine the role of the cholesterol and GPI-anchored proteins present on lipid rafts, in order to clarify the mechanism of inhibition of lymphocyte activation on PHEMA-b-PSt-b-PHEMA ABA type block copolymer(HSB) having a nanodomain-structured surface with a lamellar width of 16nm, consisting of hydrophilic poly (2-hydroxyethyl methacrylate)(PHEMA) for … More ming the A segment and hydrophobic polystyrene(PSt) forming the B segment. PSt and P(HEMA-co-St) random copolymers(HSR) were used as controls. An experiment of to determine the efficiency of interaction of lymphocytes with material surfaces was carried out by the microsphere column method. The lymphocytes were divided into three groups ; non-treated, MβCD-treated and EGPA-treated. The adherence of the lymphocytes to the material surfaces at room temperature for one hour was analyzed by electron microscopy. The non-treated lymphocytes adhering to the PSt and HSR surfaces showed spreading necrosis, whereas the lymphocytes adhering to the nanodomain-structured surfaces showed maintained shape and cytoarchitecture, similar to control lymphocytes. In the case of MβCD-and EGPA-treated lymphocytes, all the lymphocytes adhering to the PSt, HSR and nanodomain-structured surfaces exhibited maintained shape and cytoarchitecture, similar to control lymphocytes. From the above these results, it is surmised that the nanodomain-structured surface of HSB, in contrast to the PSt and HSR surfaces, allows maintenance of the structural integrity of the lipid rafts, and that activation of the Src family of tyrosine kinases is inhibited without an accumulation of lipid rafts containing the GPI-anchored proteins at the sites of lymphocyte adhesion on the nanodomain-structured surface. Less

最近，Simons K和Ikonen E提出脂筏的存在允许细胞质膜内有效的信号转导。据报道，用甲基-β-环糊精（MβCD）处理降低脂筏的胆固醇含量会干扰信号转导，而用神经酰胺内切酶II加激活剂II（EGPA）处理选择性地从脂筏的鞘糖脂中去除碳水化合物会通过糖基磷脂酰肌醇（GPI）锚定蛋白的交联损害酪氨酸激酶Src家族的激活。基于这些发现，本研究进行以确定存在于脂筏上的胆固醇和GPI锚定蛋白的作用，以阐明PHEMA-b-PSt-b-PHEMA阿坝型嵌段共聚物（HSB）抑制淋巴细胞活化的机制，所述HSB具有片层宽度为16 nm的纳米结构域结构表面，由亲水性聚（甲基丙烯酸2-羟乙酯）（PHEMA）组成， ...更多信息形成A链段和形成B链段的疏水聚苯乙烯（PSt）。PSt和P（HEMA-co-St）无规共聚物（HSR）用作对照。用微球柱法测定了淋巴细胞与材料表面的相互作用效率。将淋巴细胞分为三组：未处理组、Mβ CD处理组和EGPA处理组。通过电子显微镜分析淋巴细胞在室温下1小时对材料表面的粘附。粘附在PSt和HSR表面上的未处理的淋巴细胞显示出扩散性坏死，而粘附在纳米结构表面上的淋巴细胞显示出与对照淋巴细胞相似的保持的形状和细胞结构。在Mβ CD和EGPA处理的淋巴细胞的情况下，所有粘附于PSt、HSR和纳米结构域结构表面的淋巴细胞均表现出与对照淋巴细胞相似的形状和细胞结构。从以上这些结果，可以推测，与PSt和HSR表面相反，HSB的纳米结构域结构表面允许维持脂筏的结构完整性，并且酪氨酸激酶Src家族的活化被抑制，而在纳米结构域结构表面上的淋巴细胞粘附位点处没有含有GPI锚定蛋白的脂筏的积累。少