Exploration of the mechanism of muscle necrosis in Polymyositis.

在多发性肌炎中，细胞毒性T淋巴细胞（CTL）的浸润在具有改变的表面抗原的肌肉细胞的破坏中起关键作用。细胞溶解功能存在于CTL的细胞毒性颗粒中。一种名为穿孔素的蛋白质已被报道在肌肉细胞膜上形成圆环。我们已经检测了从小鼠CTL系纯化的穿孔素和丝氨酸酯酶以及从人血清纯化的穿孔素抑制剂的生化性质，如下所示。纯化的穿孔素在钙离子存在的情况下被肝素激活。2.红细胞溶解活性与Ca ~（2+）浓度有关。微摩尔浓度的重金属离子如Zn^2+和Fe^2+强烈抑制该酶的活性.根据最近的研究，CTL的细胞溶解分子被分成至少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，丝氨酸酯酶在小鼠CTL细胞系中的定位与穿孔素不同.在人血清中发现穿孔蛋白抑制活性。SDS PAGE显示其分子量约为500 kD，抑制与靶细胞系的结合，对裂解活性影响较小。

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.