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Postoperative portal hypertension promotes alloimmune responses in recipients after LDLT by impairing antigen presenting capacity of LSECs under sheer stress.

Research Project

Project/Area Number 23791486
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General surgery
Research Institution独立行政法人国立病院機構(呉医療センター臨床研究部) (2012)
Hiroshima University (2011)

Principal Investigator

ONOE Takashi  独立行政法人国立病院機構(呉医療センター臨床研究部), 研究室長 (90549809)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsシアストレス / 類洞内皮細胞 / 抗原提示 / 免疫寛容 / 類同内皮細胞
Research Abstract

It has been reported that portal hypertension leads to liver sinusoid cells including liver sinusoidal endotherial cells (LSECs), which are supposed to have tolerogenic capacity. We found that the incidence of acute rejection episode was significantly higher in portal hypertension patients after living-donor liver transplantation (LDLT). This fact prompted us to investigate the influence of postoperative portal vein pressure (PVP) on alloimmune response in recipient after LDLT. To investigate mechanism, we performed allogeneic co-culture assay using 70% hepatectomized (HTx) mouse model with or without porto-systemic shunt. In this assay, 3 days after HTx, digested whole hepatic constituent cells (HCs) of Balb/c mice were co-cultured with allogeneic B6 splenocytes, and B6 T-cell proliferation was quantified. Further, we performed phenotypic analysis of the LSECs and dendritic cells in the livers of these mice. The co-culture assay revealed that Balb/c HCs from HTx mice without shunt ind … More uced a significantly higher anti-Balb/c response of B6 T cells than those from untreated mice. However, this accelerated B6 T-cell response was significantly reduced in HTx mice with shunt. Phenotypic analysis revealed that LSECs from HTx mice without shunt significantly down-regulated their expressions of MHC class II, while those from Htx mice with shunt recovered their expression of MHC class II. The phenotype of dendritic cells showed no significant change. These results suggest that postoperative portal hypertension promotes alloimmune responses in recipients after LDLT, at least in part, by impairing antigen presenting capacity of LSECs. We then applied a continuous portal infusion of prostaglandin E1 (PGE1) for portal decompression to the treatment of LDLT recipients with small-for-size grafts and investigated the impact of this treatment on post-operative alloimmune responses in patients. The temporal portal infusion of PGE1 significantly attenuated portal hypertension as well as anti-donor T cell responses and clinical rejection In conclusion, our findings present a novel concept to prevent an acceleration of alloimmune responses by controlling portal vein pressure after LDLT. Less

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (28 results)

All 2013 2012 2011

All Journal Article (9 results) (of which Peer Reviewed: 3 results) Presentation (19 results)

  • [Journal Article] Attenuation of Portal Hypertension by Continuous Portal Infusion of PGE1 and Immunologic Impact in Adult-to-Adult Living-Donor Liver Transplantation.2013

    • Author(s)
      Onoe T., Tanaka Y., Ide K., Ishiyama K., Oshita A., Kobayashi T., Amano H., Tashiro H., and Ohdan H.
    • Journal Title

      Transplantation

      Volume: 95(12) Pages: 1521-1527

    • Related Report
      2012 Final Research Report
  • [Journal Article] Surgical treatment for portosystemic encephalopathy in patients with liver cirrhosis: Occlusion of portosystemic shunt in combination with splenectomy.2013

    • Author(s)
      Tashiro H., Ide K., Amano H., Kobayashi T., Onoe T., Ishiyama K., Kuroda S., Tazawa H., Kono H., Aikata H., Takahashi S., Chayama K., and Ohdan H.
    • Journal Title

      Hepatol Res.

      Volume: 43(3) Pages: 249-54

    • NAID

      10031183466

    • Related Report
      2012 Final Research Report
  • [Journal Article] Attenuation of Portal Hypertension by Continuous Portal Infusion of PGE1 and Immunologic Impact in Adult-to-Adult Living-Donor Liver Transplantation.2013

    • Author(s)
      Onoe T
    • Journal Title

      Transplantation

      Volume: Epub ahead of print

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adoptive Transfer of Allogeneic Liver Sinusoidal Endothelial Cells Specifically Inhibits T Cell Responses to Cognate Stimuli2012

    • Author(s)
      Banshodani M., Onoe T., Shishida M., Tahara H., Hashimoto S., Igarashi Y., Tanaka Y., and Ohdan H.
    • Journal Title

      Cell Transplant

      Volume: (Epub ahead of print)

    • Related Report
      2012 Final Research Report
  • [Journal Article] Optimization of immunosuppressive therapy based on a multiparametric mixed lymphocyte reaction assay reduces infectious complications and mortality in living donor liver transplant recipients.2012

    • Author(s)
      Tanaka Y., Tashiro H., Onoe T., Ide K., Ishiyama K., and Ohdan H.
    • Journal Title

      Transplant Proc.

      Volume: 44(2) Pages: 555-9

    • Related Report
      2012 Final Research Report
  • [Journal Article] 過小グラフト肝移植時のシアストレスによる肝由来免疫抑制能の破綻とその制御法に与えるシクロスポリンの影響2012

    • Author(s)
      尾上 隆司
    • Journal Title

      今日の移植

      Volume: 25 Pages: 491-494

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Adoptive transfer of allogeneic liver sinusoidal endothelial cells specifically inhibits T cell responses to cognate stimuli.2012

    • Author(s)
      Banshodani M
    • Journal Title

      Cell Transplant.

      Volume: Epub ahead of print

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of immune responses by nonimmunogenic oligodeoxynucleotides with high affinity for high-mobility group box proteins (HMGBs).2011

    • Author(s)
      Yanai H., Chiba S., Ban T., Nakaima Y., Onoe T., Honda K., Ohdan H., and Taniguchi T.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 108(28) Pages: 11542-7

    • Related Report
      2012 Final Research Report
  • [Journal Article] Suppression of immune responses by nonimmunogenic oligodeoxynucleotides with high affinity for high-mobility group box proteins (HMGBs)2011

    • Author(s)
      Yanai H, Chiba S, Ban T, Nakaima Y, Onoe T, Honda K, Ohdan H, Taniguchi T.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: Jul 12;108(28) Pages: 11542-11547

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] The Impact and Mechanism of Postoperative Portal Hypertension on Alloimmune Responses After Living Donor Liver Transplantation2013

    • Author(s)
      Onoe T, Hashimoto S, Tanaka Y, Ohdan H.
    • Organizer
      Rising Star Award, The ILTS 19th Annual International Congress
    • Place of Presentation
      Sydney, Australia
    • Related Report
      2012 Final Research Report
  • [Presentation] The Impact and Mechanism of Postoperative Portal Hypertension on Alloimmune Responses After Living Donor Liver Transplantation.2013

    • Author(s)
      Onoe T
    • Organizer
      The ILTS 19th Annual International Congress
    • Place of Presentation
      Sydney, Australia
    • Related Report
      2012 Annual Research Report
  • [Presentation] Liver Sinusoidal Endothelial Cells of Small-for-Size Grafts Lose Their Immunosuppressive Function Against Allogeneic T Cells2012

    • Author(s)
      Hashimoto S, Onoe T, Tanaka Y, Ohdan H.
    • Organizer
      American Transplantation Congress 2012American Transplantation Congress 2012
    • Place of Presentation
      Boston, USA
    • Related Report
      2012 Final Research Report
  • [Presentation] Impact of postoperative portal hypertension on alloimmune responses after living donor liver transplant2012

    • Author(s)
      Tanaka Y, Onoe T, Hashimoto S, Ohdan H. et al.
    • Organizer
      24th International congress of the transplantation society
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2012 Final Research Report
  • [Presentation] 肝過小グラフトにおける免疫応答亢進メカニズムの解析2012

    • Author(s)
      橋本慎二,尾上隆司,田中友加,大段秀樹 他
    • Organizer
      第39回日本臓器保存生物医学会学術集会
    • Place of Presentation
      福島
    • Related Report
      2012 Final Research Report
  • [Presentation] 門脈圧亢進下での拒絶反応更新メカニズムの解析2012

    • Author(s)
      橋本慎二,尾上隆司,田中友加,大段秀樹 他
    • Organizer
      第48回日本移植学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Final Research Report
  • [Presentation] 過小グラフトにおける肝由来免疫寛容性の解析2012

    • Author(s)
      橋本慎二,尾上隆司,田中友加,大段秀樹 他
    • Organizer
      第30回日本肝移植研究会
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Presentation] 過小グラフトにおける肝由来免疫寛容性の解析2012

    • Author(s)
      橋本慎二
    • Organizer
      第30回日本肝移植研究会
    • Place of Presentation
      福岡,日本
    • Related Report
      2012 Annual Research Report
  • [Presentation] Liver Sinusoidal Endothelial Cells of Small-for-Size Grafts Lose Their Immunosuppressive Function Against Allogeneic T Cells.2012

    • Author(s)
      Hashimoto S
    • Organizer
      American Transplantation Congress
    • Place of Presentation
      Boston, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Impact of postoperative portal hypertension on alloimmune responses after living donor liver transplant.2012

    • Author(s)
      Tanaka Y
    • Organizer
      24th International congress of the transplantation society
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2012 Annual Research Report
  • [Presentation] 門脈圧亢進下での拒絶反応更新メカニズムの解析2012

    • Author(s)
      橋本慎二
    • Organizer
      第48回日本移植学会総会
    • Place of Presentation
      名古屋,日本
    • Related Report
      2012 Annual Research Report
  • [Presentation] 肝過小グラフトにおける免疫応答亢進メカニズムの解析2012

    • Author(s)
      橋本慎二
    • Organizer
      第39回日本臓器保存生物医学会学術集会
    • Place of Presentation
      福島,日本
    • Related Report
      2012 Annual Research Report
  • [Presentation] Continuous portal infusion of PGE1 attenuates portal hypertension and alloimmune responses in adult-to-adult living donor liver transplantation2011

    • Author(s)
      Onoe T, Hashimoto S, Tanaka Y, Ohdan H. et al.
    • Organizer
      Congress of Asia Society of Transplantation 2011
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2011-09-25
    • Related Report
      2012 Final Research Report
  • [Presentation] 過小グラフトを用いた生体部分肝移植に対するPGE門脈持続注入療法の有用性の検討2011

    • Author(s)
      尾上隆司,橋本慎二,田中友加,大段秀樹 他
    • Organizer
      第29回日本肝移植研究会
    • Place of Presentation
      仙台
    • Year and Date
      2011-07-21
    • Related Report
      2012 Final Research Report 2011 Research-status Report
  • [Presentation] 生体部分肝移植後のPGE1門脈注入療法を用いた過小グラフト症候群治療の検討2011

    • Author(s)
      尾上隆司,橋本慎二,田中友加,大段秀樹 他
    • Organizer
      第111回日本外科学会定期学術集会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-26
    • Related Report
      2012 Final Research Report
  • [Presentation] Continuous PGE1 injection via the portal vein for small-for-size graft improves graft function and survival in adult-to-adult living donor liver transplantation2011

    • Author(s)
      Onoe T, Hashimoto S, Tanaka Y, Ohdan H. et al.
    • Organizer
      American Transplant Congress 2011
    • Place of Presentation
      Philadelphia, USA
    • Year and Date
      2011-04-30
    • Related Report
      2012 Final Research Report
  • [Presentation] Continuous PGE1 injection via the portal vein for small-for-size graft improves graft function and survival in adult-to-adult living donor liver transplantation.2011

    • Author(s)
      Onoe T
    • Organizer
      American Transplant Congress
    • Place of Presentation
      Philadelphia, USA
    • Related Report
      2011 Research-status Report
  • [Presentation] 生体部分肝移植後のPGE1門脈注入療法を用いた過小グラフト症候群治療の検討.2011

    • Author(s)
      尾上 隆司
    • Organizer
      第111回日本外科学会定期学術集会
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] Continuous portal infusion of PGE1 attenuates portal hypertension and alloimmune responses in adult-to-adult living donor liver transplantation2011

    • Author(s)
      Onoe T
    • Organizer
      Congress of Asia Society of Transplantation, 2011
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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