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Treatment of Inflammmation by Purified Human Proteinase Inhibitor.

Research Project

Project/Area Number 63570430
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionNiigata University

Principal Investigator

ASAMI Tadashi  Niigata University School of Medicine, Associate Professor, 医学部, 助教授 (40018932)

Co-Investigator(Kenkyū-buntansha) TOYABE Shin  Niigata University School of Medicine, Assistant, 医学部附属病院, 医員
西原 亨  新潟大学, 医学部, 助手 (10183542)
Project Period (FY) 1988 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1990: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1988: ¥800,000 (Direct Cost: ¥800,000)
Keywordsalpha2-macroglobulin / Nephrotic syndrome / Cell mediated immunity / Proteinase inhibitor / Treatment / ネフロ-ゼ症候群 / メロマクログロブリン / 免疫抑制作用 / プロテアーゼインヒビター / α2マクログロブリン
Research Abstract

Inhibitory activity of plasma on thermolysin, a bacterial proteinase inhibitor, was significantly higher in patients with Idiopathic Nephrotic Syndrome (INS) at relapse than in those in remission, chance proteinuria and/or hematuria and control subjecets. Sephadex G-200 gel-chromatography of plasma revealed the thermolysin inhibitory activity confined in the large molecular fractions, and Sephacryl S-300 chromatography, performed to purify alpha2-macroglobulin ( alpha2-MU) from human plasma, demonstrated the coincidence of the thermolysin inhibitory acitivity with alpha2-MU. These results suggest that the increased thermolysin ihnibitory activity of nephrotic plasma alpha2-MU contributes as a defense against possible invasion pathogens by inactivating proteinases elaborated by these organisms.
alpha2-MU was examined for deposition in kidney tissue, using FITC-labelled anti-human alpha2-MU antibody (goat). A four-year-old male, exhibiting steroid refractory nephrotic syndrome, was found … More to have diffuse deposition of alpha2-MU in the glomeruli which showed diffuse mesangial proliferation and partial hyalinizati on by light microscopy. Administration of Camostat mesillate, a commercially available synthetic proteinase inhibitor, was started and he responded well to the therapy. Granular deposition of alpha2-MU was demonstrated in the mesangium of mice after the intraperitoneal injection of alpha2-MU. The deposition of alpha2-MU in the glomeruli may directly suggest the participation of proteinase (s) and proteinase inhibitor (s) in the inflammatory processes.
In INS, proteinase inhibitory activity was significantly decreased when calculated per one mole of alpha2-MU, implicating a reduced proteinase inhibiting capacity of alpha2MU. The decreased proteinase inhibiting capacity of alpha2-MU was significantly associated with the inhibitory activity of plas ma on normal lymphocyte blastogenesis. Purified alpha2-MU complexed with chymotrypsin, intensively inhibited normal lymphocyte blastogenesis, induced by Concanavalin A, as compared to free alpha2-MU. Vascular permeability induced by nephrotic plasma was slightly ameliorated by the administration of purified alpha2-MU. Less

Report

(4 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • 1988 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] 浅見 直,西原 亨,堺 薫: "血漿中α2ーmacroglobulinのproteinase inhibitor活性測定の基礎的検討" 日本小児科学会雑誌. 92. 1087-1091 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 浅見 直,西原 亨,中野 徳,堺 薫: "賢疾患における血漿中非複合体型α2ーmacrogloblinによるプロテア-ゼインヒビタ-活性の検討" 日本小児科学会雑誌. 92. 1091-1094 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 浅見 直,西原 亨,林 三樹夫,堺 薫: "特発性ネフロ-ゼ症候群における血漿中α2ーmacroglobulinのプロテア-ゼインヒビタ-活性と細胞性免疫抑制作用の関連" 日本賢臓学会雑誌. 30. 935-941 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 浅見 直,西原 亨,林 三樹夫,堺 薫: "血中α1ーantichymotrypsin活性測定法の基礎的検討と賢疾患における変動の意義" 日本小児科学会雑誌. 92. 1889-1893 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 浅見 直,西原 亨,林 三樹夫,堺 薫: "Plasma exchangeで得られた血漿からのα2ーmacroglobulinの分離精製とそのプロテア-ゼインヒビタ-作用" 基礎と臨床. 22. 6318-6322 (2988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 浅見 直,西原 亨,藤井 美恵子,堺 薫: "特発性ネフロ-ゼ症候群における血漿α1ーproteinase inhibitor活性の低下" 日本賢臓学会雑誌. 31. 301-308 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 浅見 直,鳥谷部 森,橋本 尚士,堺 薫: "小児特発性ネフロ-ゼ症候群における血中グルタチオン." 日本賢臓学会雑誌. 32. 13-18 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Tadashi Asami,Tohru Nishihara,Tokushi Nakano,Kaoru Sakai: "Increased proteinase inhibitory activity on thermolysin in idiopathic nephrotic syndrome." Acta Medica et Biologica. 38. 41-44 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Tadashi Asami,Tohru Nishihara,Kaoru Sakai: "Plasma α1ーantichymotrypsin activity in renal diseaes of childhood." Acta Medica et Biologica. 38. 91-95 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Tadashi, Asami, Tohru, Nishigara, Tokushi, Nakano, Kaoru, Sakai: "Increased proteinase inhibitory activity on thermolysin in idiopathic nephrotic syndrome." Acta Medica et Bilogica. 38(1). 41-44 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Tadashi, Asami, Tohru, Nishihara, Kaoru, Sakai: "alpha1-antichymotrypsin activity in renal diseases of childhood." Acta Medica et Biologica. 38(2). 91-95 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 浅見 直,鳥谷部 森,橋本 尚士,堺 薫: "小児特発性ネフロ-ゼ症候群における血中グルタチオン." 日本腎臓学会雑誌. 32. 13-18 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tadashi Asami,Tohru Nishihara,Tokushi Nakano,Kaoru Sakai: "Increased proteinase inhibitory activity on thermolysin in idiopathic nephrotic syndrome.Acta Medica et Biologica,38(1):4" Acta Medica et Biologica. 38. 41-44 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tadashi Asami,Tohru Nishihara,Kaoru Sakai: "Plasma α1ーantichymotrypsin activity in renal diseaes of childhood." Acta Medica et Biologica. 38. 91-95 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 浅見直,鳥谷部森,橋本尚士,堺薫: "小児特発性ネフロ-ゼ症候群における血中グルタチオン" 日本腎臓学会雑誌. 32. 13-18 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] 浅見直: 日本小児科学会雑誌. 92. 1087-1091 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 浅見直: 日本小児科学会雑誌. 92. 1091-1094 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 浅見直: 日本腎臓学会雑誌. 30. 935-941 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 浅見直: 日本小児科学会雑誌. 92. 1889-1893 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 浅見直: 基礎と臨床. 22. 6318-6322 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 浅見直: 日本腎臓学会雑誌. 31. 301-308 (1989)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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