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血管炎発症モデルにおけるCX3C-ケモカイン,Fractalkineの関与

Research Project

Project/Area Number 13877075
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field 内科学一般
Research InstitutionKyoto University

Principal Investigator

梅原 久範  京都大学, 医学研究科, 助教授 (70247881)

Co-Investigator(Kenkyū-buntansha) 今井 俊夫  京都大学, カン研究所, 所長
三森 恒世 (三森 経世)  京都大学, 医学研究科, 教授 (10157589)
堂前 尚親  大阪歯科大学, 歯学部, 教授 (60115889)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywords血管炎 / fractalkine / モデルマウス / ケモカイン / 血管内皮細胞
Research Abstract

Fractalkineは活性化血管内皮細胞上に発現する膜型ケモカインである.我々はfractalkine receptor (CX3CR1)を世界に先駆けて同定し,CD14+単球,CD16+NK細胞,CD8+T細胞上に発現していること,およびfractalkineが従来のケモカインと異なり接着分子として作用することを報告した(Imai, Cell91:521-530,1997).咋年度に引き続き,LPS投与によるマウス血管炎モデルあるいはMRL/lprマウスにおける抗fractalkine抗体による血管炎予防効果の検討を行った.単球やNK細胞と血管内皮細胞との接着や内皮傷害の基礎的検討により,1)可溶型fractalkineは単球のfibonectinやICAM-1に対する接着をも増強した.2)fractalkine遺伝子導入したECV細胞株を用いた検討より,細胞膜上に発現したfractalkineが有意に単球やNK細胞の接着を増強した.3)fractalkineは濃度依存性にNK細胞の抗腫瘍細胞殺傷能を増強し,fractalkine発現ECV細胞やヒト胎児血管内皮細胞を著明に傷害した.4.マウス腹腔内にLPSを500μg投与すると,ほぼ前例がエンドトキシンショックと全身臓器の血管炎を発症し死亡するが,抗fractalkine抗体を24時間前およびLPSと同時に腹腔内投与すると,70%のマウスが生存した.これらの結果は,炎症に伴い産生されたサイトカインにより活性化した血管内皮細胞がfractalkineを発現し,単球やNK細胞の接着を誘導し血管炎を誘導していることを示している.抗fractalkine抗体は,この作用を抑制し,血管炎発症を阻止しうる可能性を強く示唆している.

Report

(2 results)
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Umehara, H: "Role for adapter proteins in costimulatory signals of CD2 and IL-2 on NK cell activation"Mol.Immunol.. 38. 587-596 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tanaka, Y: "H-Ras/Mitogen-activated protein kinase pathway inhibits integrin-mediated adhesion and induces apoptosis in osteoblasts"J.Biol.Chem.. 277. 21446-21452 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nishimura, M.: "Dualfunctions of fractalkine/CX3CR1 in trafficking of circulating cytotoxic effector lymphocytes that are defined by CX3CR1"J.Immunol.. 168. 6173-6180 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kondo, T.: "Vesnarinone causes oxidative damage by inhibiting catalase function through ceramide action in myeloid cell apoptosis"Mol.Pharm.. 61. 620-627 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kondo, T.: "Control of ceramide-induced apoptosis by IGF-1 : involvement of PI-3 kinase, caspase-3 and catalase"Cell Death Differnt. 9. 682-692 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawase, M.: "Increase of ceramide in adriamycin-induced HL-60 cell apoptosis : detection by a novel anti-ceramide antibody"BBA. 1584. 104-114 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Umehara, H.: "Fractalkine and vascular injury"Trends Immunol.. 22. 602-607 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Umehara. H.: "Fractalkine, a CX3C-chemokine, functions predominantly as an adhesion molecule in monocytic cell line THP-1"Immunol. Cell Biol.. 79. 298-302 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Umehara, H.: "The role of fractalkine in leukocyte adhesion and migration, and vascular injury"Drug News & Perspectives. 14. 460-464 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Umehara, H.: "Role for adapter proteins in costimulatory signals of CD2 and IL-2 on NK cell activation"Mol. Immunol.. 38. 587-596 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 梅原久範: "フラクタルカインの基礎と臨床"臨床免疫. 35. 353-359 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 梅原久範: "フラクタルカイン"臨床検査. 45. 73-76 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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