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2007 Fiscal Year Annual Research Report

異種移植の遅延型拒絶反応およびレトロウイルスの制御

Research Project

Project/Area Number 18390346
Research InstitutionOsaka University

Principal Investigator

宮川 周士  Osaka University, 医学系研究科, 准教授 (90273648)

Co-Investigator(Kenkyū-buntansha) 岡部 勝  大阪大学, 微生物研究所, 教授 (30089875)
宮沢 孝幸  京都大学, ウイルス研究所・附属新興ウイルス感染症研究センター・病態解明チーム, 特別教育研究准教授 (80282705)
文元 雄一  大阪大学, 医学部附属病院, 非常勤医員 (20397748)
Keywordsブタfactor I / 種特異性 / 補体制御因子 / ブタレトロウイルス / 糖鎖構造解析 / DAF(CD55) / サル補体価 / H-D抗原
Research Abstract

1. ブタの血清補体制御因子factor Iをcloningし、遺伝子配列を決定した。セリンプロテアーゼ(SP)ドメインはヒトと75%、マウスと76%、犬と60%の相同性を示した。さらに、このSP部分を膜型にし、ヒト、ブタ、犬血清で抗補体作用を調べたが、種特異性は顕著ではなかった。
2. 力ニクイザルの補体価をヒトでの方法で調べた。力ニクイサルの補体価は、C4を除き、一般にヒト補体価よりも高かった。DAFはブタ赤血球の溶血抑制率で、ヒトおよびサルの補体にほぼ同程度<17%血清で、約60-70%抑制>の補体制御機能を示した。
3. α-Galをknockout(KO)したブタ血管内皮(PEC)とnormal内皮をレクチンブロットで比較検討した。KO血管内皮では、normalに比し、GSI-B4のみならず、GSI,GSI-A4,BPL,SBAの反応が低下しており、α-GalNAcの発現の低下か、その後の糖鎖合成が進んでいると考えられた。
4. H-D抗原を作り出す、ブタのCMP-N-Acetylneuraminic Acidの遺伝子の一部を同定した。
5. PI-anchor型DAF、また膜貫通型(TM)型DAF:TM-HLA-G, modified influenza hemaggulutinin (HA) and MCP (delta-CYT fom)を構築、これらを発現するPECのlinesを作製、ヒト293細胞を標的細胞としたLac Z pseudo type assayと細胞障害試験を試行した。各TM型は、明らかに補体制御機能を示したが、TM型からのPERVは、PI-anchor型よりヒト血清に対して抵抗性を示さなかった。また、lipid raftと会合しないHA型及びMCP型ではその傾向が顕著であった。

  • Research Products

    (24 results)

All 2008 2007 Other

All Journal Article (10 results) (of which Peer Reviewed: 5 results) Presentation (12 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Studies of monkey complement: measurement of cynomolgus monkey CH50, ACH50, C4, C2 and C3.2008

    • Author(s)
      H Xu, and S Miyagawa
    • Journal Title

      Xenotransplantation (in press)

    • Peer Reviewed
  • [Journal Article] Analysis of the serine protease function of porcine factor I produced by liver cells for xenotransplantation.2008

    • Author(s)
      K Nakahata, S Miyagawa
    • Journal Title

      Transplant Immunol (in press)

    • Peer Reviewed
  • [Journal Article] Identification of amino acid positions involved in HLA-E expression.2008

    • Author(s)
      K Matsunami, and S Miyagawa
    • Journal Title

      J Biol (Tokyo) (in press)

    • Peer Reviewed
  • [Journal Article] Investigation of cynomolgus monkey complement2008

    • Author(s)
      H Xu, and S Miyagawa
    • Journal Title

      Transplant Proc (in press)

  • [Journal Article] Prevalence of porcine endogenous retroviruses in domestic, miniature and genetically-modified pigs in Japan2008

    • Author(s)
      T Fujimura, S Miyagawa, et. al.
    • Journal Title

      Transplantat Proc (in press)

  • [Journal Article] Molecular cloning of pig Rad51, Rad52 and Rad54 genes, which are in volved in homologous recombination machinery.2008

    • Author(s)
      K Matsunami, S Miyagawa.
    • Journal Title

      Transplant Proc (in press)

  • [Journal Article] Isolation and sequencing of pig Blm and Ubl-1/SUMO-1 genes that relate to the recombination machinery.2008

    • Author(s)
      K Matsunami, S Miyagawa.
    • Journal Title

      Transplant Proc (in press)

  • [Journal Article] Cloning and in vitro anti-apoptotic effects of pig FLIPs.2008

    • Author(s)
      H Xu, and S Miyagawa
    • Journal Title

      Transplant Proc (in press)

  • [Journal Article] Cloning of pig serine proteinase inhibitor 9 (PI-9) and its use in protecting against apoptosis.2007

    • Author(s)
      K Matsunami, and S Miyagawa.
    • Journal Title

      Transplant Int 20

      Pages: 453-459

    • Peer Reviewed
  • [Journal Article] Effect of blocking the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in a rat2007

    • Author(s)
      Y lhara, S Miyagawa, et. al.
    • Journal Title

      Transplant Immunol 17

      Pages: 271-277

    • Peer Reviewed
  • [Presentation] ANALYSIS OF THE SERINE PROTEASE FUNCTION OF PORCINE FACTOR I2007

    • Author(s)
      K Nakahata, and S Miyagawa
    • Organizer
      7th Congress of the Asian Society of Transplantation
    • Place of Presentation
      Pataya, Thailand
    • Year and Date
      20071201-04
  • [Presentation] CLONING AND IN VITRO ANTI-APOPTOTIC EFFECTS OF PIG FLIPs2007

    • Author(s)
      S Miyagawa, et. al.
    • Organizer
      7th Congress of the Asian Society of Transplantation
    • Place of Presentation
      Pataya, Thailand
    • Year and Date
      20071201-04
  • [Presentation] EFFECTS OF PLASMINOGEN ACTIVATOR INHIBITOR TYPE 2 OVEREXPRESSION ON NK CELL-MEDIATED LYSIS2007

    • Author(s)
      S Miyagawa, et. al.
    • Organizer
      7th Congress of the Asian Society of Transplantation
    • Place of Presentation
      Pataya, Thailand
    • Year and Date
      20071201-04
  • [Presentation] ISOLATION AND SEQUENCING OF PIG BLM AND UBL-1/SUMO-1 GENES THATRELATE TO THE RECOMBINATION MACHINERY.2007

    • Author(s)
      K. Matsunami, S Miyagawa
    • Organizer
      7th Congress of the Asian Society of Transplantation
    • Place of Presentation
      Pataya, Thailand
    • Year and Date
      20071201-04
  • [Presentation] MOLECULAR CLONING OF PIG RAD51, RAD52 and RAD54 GENES, WHICH AREINVOLVED IN THE HOMOLOGOUS RECOMBINATION MACHINERY.2007

    • Author(s)
      K. Matsunami, S Miyagawa
    • Organizer
      7th Congress of the Asian Society of Transplantation
    • Place of Presentation
      Pataya, Thailand
    • Year and Date
      20071201-04
  • [Presentation] The importance of pig dolichy-phosphate mannosyltransferase for preventing porcine endogenous retrovirus transmission to human cells2007

    • Author(s)
      S Miyagawa, et. al.
    • Organizer
      The 9th Congress of International Congress for Xenotransplantation (Joint Conference)
    • Place of Presentation
      Minneapolis, USA
    • Year and Date
      20070915-20
  • [Presentation] Critical positions for expression of HLA-E2007

    • Author(s)
      K Matsunami, and S Miyagawa
    • Organizer
      The 9th Congress of International Congress for Xenotransplantation (Joint Conference)
    • Place of Presentation
      Minneapolis, USA
    • Year and Date
      20070915-20
  • [Presentation] Studies on monkey complement: a titration of cynomolgus monkey CH50, ACH50, C4, C2 and C32007

    • Author(s)
      H Xu, and S Miyagawa
    • Organizer
      The 9th Congress of International Congress for Xenotransplantation (Joint Conference)
    • Place of Presentation
      Minneapolis, USA
    • Year and Date
      20070915-20
  • [Presentation] Molecular Cloning and analysis of serine protease function of porcine factor I2007

    • Author(s)
      K Nakahata, and S Miyagawa
    • Organizer
      The 9th Congress of International Congress for Xenotransplantation (Joint Conference)
    • Place of Presentation
      Minneapolis, USA
    • Year and Date
      20070915-20
  • [Presentation] Prevalence of porcine endogenous retroviruses in domestic, miniature and genetically-modified pigs in Japan2007

    • Author(s)
      T. Fujimura, S. Miyagawa, et. al.
    • Organizer
      The 9th Congress of International Congress for Xenotransplantation (Joint Conference)
    • Place of Presentation
      Minneapolis, USA
    • Year and Date
      20070915-20
  • [Presentation] The Development of the Genetic Modified Pig for Clinical Application2007

    • Author(s)
      S Miyagawa
    • Organizer
      Horizons in Transplantation
    • Place of Presentation
      Houston, Texas
    • Year and Date
      20070518-19
  • [Presentation] The development of the genetic-modified pig and the prevention of PERV for clinical application2007

    • Author(s)
      S Miyagawa
    • Organizer
      2007 Seoul Forum on Xenotransplantation
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2007-11-10
  • [Book] Xenotransplantation and glycomedicine. Comprehensive Glycoscience. Johannis P Kamerling (Eds.)2007

    • Author(s)
      Shuji Miyagawa
    • Total Pages
      20
    • Publisher
      ELSEVIER
  • [Remarks]

    • URL

      http://www.med.Osaka-u.ac.jp/pub/orgtrp/www/index-jp.html

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Published: 2010-02-04   Modified: 2016-04-21  

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