Strategy of macrophage-mediated xenograft rejection through inhibitory signaling to SIRP.

• Project/Area Number: 20890141
• Research Category: Grant-in-Aid for Young Scientists (Start-up)
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Hiroshima University
• Principal Investigator: IDE Kentaro Hiroshima University, 病院, 助教 (50511565)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,302,000 (Direct Cost: ¥2,540,000、Indirect Cost: ¥762,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,742,000 (Direct Cost: ¥1,340,000、Indirect Cost: ¥402,000)
• Keywords: 異種移植 / CD47 / マクロファージ / 拒絶反応 / 遺伝子導入

Research Abstract

We have previously shown that pig CD47 does not interact with human SIRPα, and that human CD47 expression inhibits phagocytosis of porcine cells by human macrophages in vitro. In this study, we investigate the potential of human CD47 expression to promote porcine cell survival in vivo.

Research Products

• [Journal Article] Determination of the precursor frequency and the reaction intensity of xenoreactive human T lymphocytes. (2010)
  • Author(s): Tahara H, Ide K, Basnet NB, Tanaka Y, Ohdan H
  • Journal Title: Xenotransplantation (in press)
  • Peer Reviewed
• [Journal Article] Immunological property of antibodies against N-glycolylneuraminic acid epitopes in cytidine monophospho-N-acetylneuraminic acid hydroxylase-deficient mice. (2010)
  • Author(s): Tahara H, Ide K, Basnet NB, Tanaka Y, Matsuda H, Takematsu H, Kozutsumi Y, Ohdan H
  • Journal Title: J Immunol 184(6) Pages: 3269-3275
  • Peer Reviewed
• [Journal Article] Immunological property of antibodies against N-glycolylneuraminic acid epitopes in cytidine monophospho-N-acetylneuraminic acid hydroxylase-deficient mice (2010)
  • Author(s): Hiroyuki Tahara
  • Journal Title: Journal of Immunology 184 Pages: 3269-3275
  • Peer Reviewed
• [Journal Article] Determination of the precursor frequency and the reaction intensity of xenoreactive human T lymphocytes (2010)
  • Author(s): Hiroyuki Tahara
  • Journal Title: Xenotransplantation (掲載決定)
  • Peer Reviewed
• [Journal Article] Engraftment of human hepatocytes in the livers of rats bearing bone marrow reconstructed with immunodeficient mouse bone marrow cells. (2008)
  • Author(s): Igarashi Y, Tateno C, Tanaka Y, Tachibana A, Utoh R, Kataoka M, Ohdan H, Asahara T, Yoshizato K
  • Journal Title: Xenotransplantation Pages: 235-245
  • Peer Reviewed
• [Journal Article] Engraftment of human hepatotytes in the livers of rats bearing bone marrow reconstructed with immunodeficient mouse bone marrow cells (2008)
  • Author(s): Igarashi Yuka
  • Journal Title: Xenotransplantation 15 Pages: 235-245
  • Peer Reviewed
• [Presentation] ブタ-ヒト異種間T細胞応答におけるCD47-SIRPシグナルの役割 (2010)
  • Author(s): 田原裕之
  • Organizer: 第13回日本異種移植研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-14
• [Presentation] 健常人におけるαGalおよびN-glycolylneuraminic acid (NeuGc)に対する自然抗体価と細胞傷害性の比較 (2010)
  • Author(s): Nabin Basnet
  • Organizer: 第13回日本異種移植研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-14
• [Presentation] 健常人におけるα-GalおよびN-glycolylneuraminic acid(NeuGc)に対する自然抗体価と細胞傷害性の比較 (2010)
  • Author(s): Nabin Basnet
  • Organizer: 第13回日本異種移植研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-14
• [Presentation] 異種移植における異種抗原N-Glycolylneuraminic acid(NeuGc)の抗原性 (2010)
  • Author(s): 田原裕之
  • Organizer: 第37回膵・膵島移植研究会
  • Place of Presentation: 宇都宮
  • Year and Date: 2010-03-12
• [Presentation] 異種移植における異種抗原N-Glycolylneuraminic acid(NeuGc)の役割 (2009)
  • Author(s): 田原裕之
  • Organizer: 第45回日本移植学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-17
• [Presentation] N-glycorylneuraminic acid is recognized by naturally occurring cytotoxic human xenoantibodies (2009)
  • Author(s): Nabin Basnet
  • Organizer: 第45回日本移植学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-17
• [Presentation] Evidence of cytotoxicity of non-Gal antibodies against N-glycolyl neuraminic acid determinants in xenotransplantation by using CMAH-/- mice (2009)
  • Author(s): Hiroyuki Tahara
  • Organizer: American Transplantation Congress
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-06-03
• [Presentation] Evidence of cytotoxicity of non-Gal antibodies against N-glycolylneuraminic acid determinants in xenotransplantation by using CMAH-/- mice (2009)
  • Author(s): 田原裕之
  • Organizer: American Transplantation Congress
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-06-03
• [Presentation] Deficiency of N-glycolyl neuraminic acid besides Galα1, 3Gal on xenogeneic cells attenuates cytotoxocity of human natural antibodies (2009)
  • Author(s): Nabin Basnet
  • Organizer: American Transplantation Congress
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-05-30
• [Presentation] Deficiency of N-glycolylneuraminic acid besides Gal_α1,3Gal on xenogeneic cells attenuates cytotoxocity of human natural antibodies (2009)
  • Author(s): Nabin Basnet
  • Organizer: American Transplantation Congress
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-05-30
• [Presentation] N-glycolylneuraminic acid- A novel target for rejection in islet xenotransplantation- (2009)
  • Author(s): Hiroyuki Tahara
  • Organizer: Joint Conference of CTS&JSOPMB
  • Place of Presentation: Okayama, Japan
  • Year and Date: 2009-04-21
• [Presentation] 健常人におけるα-GalおよびN-glycolylneuraminic acid(NeuGc)に対する自然交代価と細胞障害性の比較 (2009)
  • Author(s): Nabin Basnet
  • Organizer: 第12回日本異種移植研究会
  • Place of Presentation: 鹿児島
  • Year and Date: 2009-03-07
• [Presentation] 異種抗原N-Glycolyl neuraminic acid(NeuGc)は異種島移植における拒絶の標的となる (2009)
  • Author(s): 田原裕之
  • Organizer: 第12回日本異種移植研究会
  • Place of Presentation: 鹿児島
  • Year and Date: 2009-03-07
• [Presentation] 異種抗原N-Glycolylneuraminic acid(NeuGc)は異種島移植における拒絶の標的となる (2009)
  • Author(s): 田原 裕之
  • Organizer: 第12回日本異種移植研究会
  • Place of Presentation: 鹿児島
  • Year and Date: 2009-03-07
• [Presentation] Comparative detecton of cytotoxic natural antibody againstα-Gal and NeuGc epitopes in healthy human sera (2008)
  • Author(s): Nabin Basnet
  • Organizer: 第44回日本移植学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2008-09-21
• [Presentation] CD47-SIRPシステムを介した異種T細胞性拒絶反応制御の可能性 (2008)
  • Author(s): 田原裕之
  • Organizer: 第44回日本移植学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2008-09-21
• [Presentation] Comparative detecton of cytotoxic natural antibody against α-Gal and NeuGc epitopes in healthy human sera (2008)
  • Author(s): Basnet Nabin
  • Organizer: 第44回日本移植学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2008-09-21
• [Presentation] Human CD47 on porcine antigen presenting cells have possivility of preventing T cell-mediated xenograft rejection through inhibitory signaling to SIRPαXXII (2008)
  • Author(s): Kentaro Ide
  • Organizer: International Congress of The Transplantation Society
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2008-08-13
• [Presentation] Human CD47 on porcine antigen presenting cells have possivility of preventing T cell-mediated xenograft rejection through inhibitory signaling to SIRPα (2008)
  • Author(s): Ide Kentaro
  • Organizer: XX II International Congress of The Transplantation Society
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2008-08-13
• [Presentation] In Vitro and In Vivo Evidence of Cytotoxocity of Antibodies Against N-Glycolylneuraminic Acid (NeuGc) in Xenotransplantation American (2008)
  • Author(s): Hiroyuki Tahara
  • Organizer: Transplant Congress 2008
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2008-06-01
• [Presentation] Role for CD47-SIRPαSignaling in Human T Cell Proliferation in Response to Stimulation with Porcine Antigen Presenting Cells American (2008)
  • Author(s): Hirouiki Tahara
  • Organizer: Transplant Congress 2008
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2008-06-01
• [Presentation] Role for CD47-SIRPα signaling in human T cell proliferation in response to stimulation with porcine antigen presenting cells (2008)
  • Author(s): Tahara Hiroyuki
  • Organizer: American Transplant Congress 2008
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2008-06-01
• [Presentation] In vitro and in vivo evidence of cytotoxocity of antibodies against N-Glycolylneuraminic Acid(NeuGc) in xenotransplantation (2008)
  • Author(s): Tabara Hiroyuki
  • Organizer: American Transplant Congress 2008
  • Place of Presentation: Toronto, Canada