权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Exploration of the mechanism of muscle necrosis in Polymyositis.

多发性肌炎肌肉坏死机制探讨。

基本信息

批准号：
63480219
负责人：
SUGITA Hideo
金额：
$ 2.43万
依托单位：
National Center of Neurology and Psychiatry (NCNP)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

In polymyositis, the infiltration of cytotoxic T-lymphocyte (CTL) plays a key role in the destruction of muscle cells with altered surface antigen. The cytolytic function resides in cytotoxic granules in CTL. A protein, named perforin has been reported to form circular rings on muscle cell membranes. The formation of rings is followed by lysis of the muscle cell due to serine esterases.We have examined the biochemical properties of perforin and serine eserases purified from mouse CTL line and also purified perforin inhibitors from human serum as illustrated below.1. The purified perforin is activated by heparin in the presence of calcium ion.2. The lytic activity of erythrocyte was dependent on the concentration of Ca ion. The activity was strongly inhibited by micromolar concentration of heavy metal ions, such as Zn^<2+> and Fe^<2+>.3. According to recent studies, the cytolytic molecules of CTL are divided into at least 3 components, i.e., pore-forming protein, perforin, serine esterase and tumor necrosis factor-like cytotoxin. Among them, the localization of serine esterase was found to be different from that of perforin in mouse CTL line.4. Perforin inhibitory activity was found in human serum. It had a molecular weight of approximately 500 kD on SDS PAGE and inhibited the binding to the target cell line, less affecting the lytic activity.

在多发性肌炎中，细胞毒性T淋巴细胞(CTL)的渗透在表面抗原改变的肌肉细胞的破坏中起着关键作用。CTL的细胞毒作用存在于细胞毒颗粒中。据报道，一种名为穿孔素的蛋白质可以在肌肉细胞膜上形成环形环。在形成环之后，肌肉细胞由于丝氨酸酯酶的裂解而形成。我们研究了从小鼠CTL系中纯化的穿孔素和丝氨酸酯酶以及从人血清中纯化的穿孔素抑制剂的生化性质，如下所示。纯化的穿孔素在有钙离子存在的情况下被肝素激活。红细胞的溶解活性依赖于钙离子的浓度。微摩尔浓度的重金属离子，如Zn~(2+)、Fe~(2+)和Gt~(2+)对酶有强烈的抑制作用。根据最近的研究，CTL的细胞溶解分子至少可分为3个组分，即孔形成蛋白、穿孔素、丝氨酸酯酶和肿瘤坏死因子样细胞毒素。其中，丝氨酸酯酶与穿孔素在小鼠CTL中的定位不同。在人血清中发现穿孔素抑制活性。经SDS-PAGE分析，其相对分子质量约为500kD，能抑制与靶细胞的结合，对裂解活性影响不大。