| Project/Area Number |
63480219
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | National Center of Neurology and Psychiatry (NCNP) |
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Principal Investigator |
SUGITA Hideo NCNP, National Institute of Neuroscience (NIN), Director, 神経研究所, 所長 (80009951)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKAHARA Toshifumi NCNP, NIN, Division of Neuromuscular Research, Staff Researcher, 神経センター神経研究所・疾病研究第一部, 研究員 (60207339)
ISHIURA Shoichi NCNP, NIN, Division of Neuromuscular Research, Section Chief, 神経センター神経研究所・疾病研究第一部, 室長 (10158743)
ARAHATA Kiichi NCNP, NIN, Division of Neuromuscular Research, Section Chief, 神経センター神経研究所・疾病研究第一部, 室長 (30053325)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1989: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1988: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | 多発性筋炎 / 細胞障害性T-リンパ球 / パ-フォリン / セリンエステラ-ゼ / パ-フォリンインヒビタ- / パーフォリン / セリンエステラーゼ |
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| Research Abstract |
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.
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