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多光子励起顕微鏡と量子ドットを用いたANCA関連血管炎の腎臟イメージング解析

Research Project

Project/Area Number 21790377
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionChiba University

Principal Investigator

長尾 朋和  Chiba University, 医学(系)研究科(研究院), その他 (90451757)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords免疫学 / ANCA関連血管炎 / 糸球体腎炎 / 量子ドット / 自己抗体 / 好中球
Research Abstract

1.多光子励起顕微鏡を用いたマウス腎糸球体観察法の確立
昨年度作製法を確立したmaMPOを量子ドット(Qdot)で標識したもの(maMPO-Qdot)を調製し、簡易的に倒立型蛍光顕微鏡で、maMPO-Qdot投与後におけるその腎臓内分布を凍結切片上で観察。その結果、微弱ながら腎臓におけるmaMPO-Qdotの蛍光を観察したが、傾向強度は微弱であった。そこで現在、量子ドット以外に通常の有機蛍光化合物も利用したmaMPOをラベリングしたmaMPOの生体内分布を継続中。
2.maMPOの腎炎誘導活性評価
maMPOとLPSの併用によるC57BL/6マウスの半月体性糸球体腎炎モデルについて、腎臓切片のHE染色・PAS染色・蛍光免疫染色、腎臓中のmRNA発現の定量PCR解析を行った。その結果、LPSの単独投与によって、主に好中球と考えられるGr-1+細胞の糸球体への浸潤が見られたが、maMPOの単独投与ではそのような変化が見られなかった。また、好中球、マクロファージの浸潤に関与する接着分子ICAM-1、ケモカインKC、MCP-1などの腎臓におけるmRNA発現を検討したところ、LPSの投与によって有意に増加することを確認した。従って、LPSによる好中球浸潤に加え、maMPO投与による好中球の活性化が血管傷害の主たる原因であることが推察された。
3.In vitroにおける糸球体血管内皮細胞、maMPO、好中球の相互作用
maMPOによる糸球体血管内皮細胞の直接的活性化メカニズムに関わる新規抗原分子Moesinを同定し、maMPOがMoesinに交差反応で結合。血管内皮細胞に活性化シグナルを伝達している事を明らかにした。

Report

(2 results)
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (22 results)

All 2011 2010 2009

All Journal Article (9 results) (of which Peer Reviewed: 4 results) Presentation (13 results)

  • [Journal Article] Direct activation of glomerular endothelial cells by anti-moesin activity of anti-myeloperoxidase antibody2011

    • Author(s)
      Nagao T
    • Journal Title

      Nephrology Dialysis Transplantation

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 血管炎についての最近の話題-基礎研究の立場から-2011

    • Author(s)
      鈴木和男
    • Journal Title

      医学のあゆみ

      Volume: 236 Pages: 791-798

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Reduction of MPO-ANCA epitopes in SCG/Kj mice by 15-deoxyspergualin treatment restricted by IgG2b associated with crescentic glomerulonephritis2010

    • Author(s)
      Tomizawa K
    • Journal Title

      Rheumatology(Oxford)

      Volume: 49 Pages: 1245-1256

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ANCA関連血管炎とneutrophil extracellular traps (NETs)2010

    • Author(s)
      長尾朋和
    • Journal Title

      リウマチ科

      Volume: 43 Pages: 414-419

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Reduction of MPO-ANCA epitopes in SCG/Kj mice by 15-Deoxyspergualin treatment restricted by IgG2b associated with crescentic glomerulonephritis2010

    • Author(s)
      Kazuo Tomizawa
    • Journal Title

      Rheumatology (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Screening of epithelial cell-adhesive peptides from fibronectin loop region and its cell specificity2009

    • Author(s)
      Chiaki Kaga
    • Journal Title

      J Chem.Engineering Japan 4

      Pages: 298-302

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MPO-ANCA関連血管炎と血管内皮細胞2009

    • Author(s)
      長尾朋和
    • Journal Title

      腎と透析 68

      Pages: 89-93

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 好中球機能異常による血管炎・腎炎2009

    • Author(s)
      長尾朋和
    • Journal Title

      細胞 41

      Pages: 60-63

    • Related Report
      2009 Annual Research Report
  • [Journal Article] MPO-ANCA関連血管炎―発症機構解析・モデルマウス・新たな治療法2009

    • Author(s)
      長尾朋和
    • Journal Title

      炎症と免疫 17

      Pages: 707-713

    • Related Report
      2009 Annual Research Report
  • [Presentation] Treatments for MPO-ANCA-associated vasculitis in SCG/Kj mouse2010

    • Author(s)
      Kusunoki R
    • Organizer
      14^<th> International Congress of Immunology
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] Murine crescentic glomerulonephritis model using anti-MPO and anti-LAMP2 antibodies2010

    • Author(s)
      Nagao T
    • Organizer
      14^<th> International Congress of Immunology
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] Mechanism of neutrophil extracellular traps formation by anti-myeloperoxidase antibodies2010

    • Author(s)
      Suzuki K
    • Organizer
      14^<th> International Congress of Immunology
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] MPO-ANCA関連血管炎モデルにおけるLPSの役割2010

    • Author(s)
      長尾朋和
    • Organizer
      第21回日本生体防御学会学術集会
    • Place of Presentation
      仙台
    • Year and Date
      2010-07-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Development of murine crescentic glomerulonephritis model using anti-MPO and anti-LAMP-2 antibodies2010

    • Author(s)
      長尾朋和
    • Organizer
      Inflammation Program Seminar
    • Place of Presentation
      千葉
    • Year and Date
      2010-01-15
    • Related Report
      2009 Annual Research Report
  • [Presentation] Association of risk epitopes of MPO-ANCA with renal failure in SCG/Kj mice showing crescentic glomerulonephritis2009

    • Author(s)
      Kazuo Tomizawa
    • Organizer
      6th International Human Peroxidase Meeting
    • Place of Presentation
      North Carolina, USA
    • Related Report
      2009 Annual Research Report
  • [Presentation] MPO-ANCAが直接誘導する糸球体血管内皮細胞活性化の分子機構2009

    • Author(s)
      長尾朋和
    • Organizer
      第52回日本腎臓学会学術総会、シンポジウム
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] Risk Epitopes of MPO-ANCA in SCG/Kj mice2009

    • Author(s)
      Kazuo Tomizawa
    • Organizer
      14th International Vasculitis and ANCA Workshop
    • Place of Presentation
      Lund, Sweden Copenhagen, Denmark
    • Related Report
      2009 Annual Research Report
  • [Presentation] Dietary enrichment with eicosapentanoic acid(EPA) prevents antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis2009

    • Author(s)
      Junichi Hirahashi
    • Organizer
      14th International Vasculitis and ANCA Workshop
    • Place of Presentation
      Lund, Sweden Copenhagen, Denmark
    • Related Report
      2009 Annual Research Report
  • [Presentation] Risk Epitopes of MPO-ANCA in patients with MPA in Japan2009

    • Author(s)
      Kazuo Suzuki
    • Organizer
      14th International Vasculitis and ANCA Workshop
    • Place of Presentation
      Lund, Sweden Copenhagen, Denmark
    • Related Report
      2009 Annual Research Report
  • [Presentation] 抗MPO抗体刺激による活性化血管内皮細胞由来のケモカインの役割2009

    • Author(s)
      長尾朋和
    • Organizer
      第15回MPO研究会
    • Place of Presentation
      栃木
    • Related Report
      2009 Annual Research Report
  • [Presentation] A mouse model of pauci-immune glomerulonephritis induced by monoclonal anti-LAMP-2 antibody2009

    • Author(s)
      長尾朋和
    • Organizer
      第39回日本免疫学会総会・学術集会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] Involvement of Interleukin-6 in RPGN of SCG/Kj mice2009

    • Author(s)
      Reina Kusunoki
    • Organizer
      第39回日本免疫学会総会・学術集会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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