1998 年度実績報告書

標的臓器の分子生物学的修飾と免疫寛容

研究課題

研究課題/領域番号	09470247
研究機関	名古屋大学
研究代表者	横山逸男名古屋大学, 医学部, 講師 (60240206)
研究分担者	デルカルピオカルロス豊橋技術科学大学, エコロジー工学系, 講師 (20231053) 小林孝彰名古屋大学, 医学部, 医員林衆治名古屋大学, 医学部, 助手 (30218573)
キーワード	アポトーシス / 臓器移植 / 細胞障害 / Fas抗原 / SOD / フリーラジカル
研究概要	移植臓器となる標的臓器を分子生物学的に修飾することによって臓器受給者(レシピエントに免疫制御などの負担を課することなく、臓器移植における究極的目標である免疫寛容を確立するための実験を行った。移植臓器の細胞障害を防ぐために、細胞死、特にFas、Fas ligandによるアポトーシスのメカニズムを解析し、その上でアポトーシス抑制の可能性について探求した。その結果、標的臓器となる細胞として肝細胞および血管内皮細胞を例にとれば、前者では免疫抑制剤であるタクロリムスが示適濃度でFas抗原を抑制することがわかった。後者の血管内皮細胞については、臓器保存に伴う虚血再潅流障害の原因と考えられるフリーラジカルによるアポトーシスのメカニズムを解析した。そして抗フリーラジカル作用を有するスーパーオキサイドディスムターゼ(SOD)の役割が重要であり、遺伝子工学的手法を用い、ヒトCu、Zn-SODを標的細胞に導入しアポトーシスの抑制効果を確認することができた。このほかアポトーシス関連因子であるカルシウムの細胞内濃度推移を継時的に測定し、細胞障害との相関を確認することができ、従って抗カルシウム剤のアポトーシス抑制効果の可能性も示唆された。以上の知見から移植臓器の細胞障害をアポトーシスの観点から分子生物学的な修飾を行うことにより、免疫寛容を樹立する可能性を示すものと考えた。

研究成果

(20件)

すべてその他

すべて文献書誌 (20件)

[文献書誌] Yuji Tachi,Itsuo Yokoyama,Hiroshi Takagi: "Variability of cytotoxicity to pig cultured cells and its determinant factor in human sera." Transplantation Proceedings. 30・1. 71-73 (1997)
[文献書誌] C Koike,I Yokoyama,H Takagi: "Direct gene replacement of the mouse α(1,3)-galactosylferase gene with human α(1,2)fucosyltransferase gene:Converting α-galactosyl epitopes into H antigens" Xenotransplantation. 4. 147-153 (1997)
[文献書誌] T Kobayashi,I Yokoyama,H Takagi: "TAP1,TAP2,LMP2,DMA,and DMB genetic polymorphisms in renal transplantation." Transplantation Proceedings. 30・1. 29-30 (1997)
[文献書誌] 林衆治、横山逸男、高木弘: "同種移植及び異種移植における遺伝子制御に関する研究" 今日の移植. 11・2. 157-164 (1997)
[文献書誌] S Hayashi,I Yokoyama,H Takagi: "Establishment of complement-resistant retroviral vector by homologous restriction factor 20 gene." Gene Therapy. 5. 282-285 (1998)
[文献書誌] S Hayashi,I Yokoyama H Takagi: "Feasibility of Double-Expression Retroviral Vector Using Complement regulatory Factor Gene" Journal of Surgical Research. 78. 64-67 (1998)
[文献書誌] S Hayashi,I Yokoyama,H Takagi: "Adenovirus-mediated gene transfer to the xenogeneic liver xenotransplan-tation:the transduction of complement regulatory factor genes (DAF and HRF20)." Transplantation Proceedings. 29・4. 2211-2211 (1997)
[文献書誌] S Hayashi,I Yokoyama,H Takagi: "Effect of CTLA4-Ig gene transfer using adenoviral vector in organ and cell transplantation." Transplantation Proceedings. 29・4. 2212-2212 (1997)
[文献書誌] A Katayama,I Yokoyama,H Takagi: "Studied of alpha-Gal dependent hyperacute xenotransplant rejection using double knockout embryonic stem cells." Transplantation Proceedings. 29・4. 2262-2262 (1997)
[文献書誌] H Asano,I Yokoyama,H.Inoko,H Takagi: "Significance of tumor necrosis factor microsatellite polymorphism in renal transplantation." Tissue Antigens. 50・5. 484-488 (1997)
[文献書誌] T Nagasaka,I Yokoyama,T Muramatsu,H Takagi: "α-Galactosyl oligosaccharides conjugated with polyethylene glycol as potential inhibitors of hyperacute rejection upon xenotransplantation" Biochemical and Biophysical Research Communications. 232. 731-736 (1997)
[文献書誌] Yasutomi M,Yokoyama I,Takagi H: "Evaluation of tetrahydropyranyladriamycin as an immunosuppressant in concordant xenotransplantation" The Journal of Heart Lung Transplantation. 16・8. 283-289 (1997)
[文献書誌] S Hayashi,I Yokoyama,H Takagi: "Protection of xeno-hepatocytes from complement-mediated cytolysis by transduction with homologous restriction factor 20 gene using retroviral vector." European Surgical Research. 30・3. 161-167 (1998)
[文献書誌] A Katayama,I Yokoyama,T Muramatsu,H Takagi: "Porcinr α-1.3-galactosyltransferase:full length cDNA cloning,genomic organization,and analysis of splicing variants" Glycoconjugate Journal. 15. 583-589 (1998)
[文献書誌] K Uchiyama,H Muramatsu,I Yokoyama,T Muramatsu: "Human N-Acetylglucosamine-6^2O-Sulfotransferase Involved in the Biosynthesis of 6-Sulo Sialyl Lewis X:Molecular Cloning,chromosomal mapping,and Expression in Various Organs and Tumor Cells" The Japanese Biochemical Society. 124. 670-678 (1998)
[文献書誌] S.Hayashi,I Yokoyama,and H.Takagi: "Technique of Triple Splir-Liver Transplantation in Pigs Using Inferior Vena Cava Reconstruction and Intraoperative Intrahepatic Portosystemic Shunt" Transplantation Proceedings. 30・7. 3229-3231 (1998)
[文献書誌] S Hayashi,M.G.Lin,I Yokoyama,H Takagi: "Auxiliary orthotopic Xenogeneic Liver Transplantation Using Pigs for Fulminant Hepatic failure:With Special Reference to the Technique and Immunosuppression" Transplantation Proceedings. 30. 3836-3836 (1998)
[文献書誌] T.Nagasaka,I Yokoyama,and H.Takagi: "Inhibitory Effect of α(1,2)Fucosyltransferase Recombinant Adenoviral Vector on α Gal Expression" Transplantation Proceedings. 30. 3837-3838 (1998)
[文献書誌] 小川晴子、小林孝彰、門松健治、横山逸男、高木弘、村松喬: "異種移植における抗原の制御" Organ Biology. 5・4. 25-33 (1998)
[文献書誌] Shuji Hayashi,Takaharu,I Yokoyama Nagasaka,Taiki Kojima,Yasushi,Namii,Akio: "Combination splitting using both in situ and ex situ Techniques in triple split liver transplantation in pigs" Transplantation International. 11. 408-412 (1998)

1998 年度 実績報告書

標的臓器の分子生物学的修飾と免疫寛容

研究代表者

横山 逸男 名古屋大学, 医学部, 講師 (60240206)

研究成果

[文献書誌] Yuji Tachi,Itsuo Yokoyama,Hiroshi Takagi: "Variability of cytotoxicity to pig cultured cells and its determinant factor in human sera." Transplantation Proceedings. 30・1. 71-73 (1997)

[文献書誌] C Koike,I Yokoyama,H Takagi: "Direct gene replacement of the mouse α(1,3)-galactosylferase gene with human α(1,2)fucosyltransferase gene:Converting α-galactosyl epitopes into H antigens" Xenotransplantation. 4. 147-153 (1997)

[文献書誌] T Kobayashi,I Yokoyama,H Takagi: "TAP1,TAP2,LMP2,DMA,and DMB genetic polymorphisms in renal transplantation." Transplantation Proceedings. 30・1. 29-30 (1997)

[文献書誌] 林 衆治、横山逸男、高木 弘: "同種移植及び異種移植における遺伝子制御に関する研究" 今日の移植. 11・2. 157-164 (1997)

[文献書誌] S Hayashi,I Yokoyama,H Takagi: "Establishment of complement-resistant retroviral vector by homologous restriction factor 20 gene." Gene Therapy. 5. 282-285 (1998)

[文献書誌] S Hayashi,I Yokoyama H Takagi: "Feasibility of Double-Expression Retroviral Vector Using Complement regulatory Factor Gene" Journal of Surgical Research. 78. 64-67 (1998)

[文献書誌] S Hayashi,I Yokoyama,H Takagi: "Adenovirus-mediated gene transfer to the xenogeneic liver xenotransplan-tation:the transduction of complement regulatory factor genes (DAF and HRF20)." Transplantation Proceedings. 29・4. 2211-2211 (1997)

[文献書誌] S Hayashi,I Yokoyama,H Takagi: "Effect of CTLA4-Ig gene transfer using adenoviral vector in organ and cell transplantation." Transplantation Proceedings. 29・4. 2212-2212 (1997)

[文献書誌] A Katayama,I Yokoyama,H Takagi: "Studied of alpha-Gal dependent hyperacute xenotransplant rejection using double knockout embryonic stem cells." Transplantation Proceedings. 29・4. 2262-2262 (1997)

[文献書誌] H Asano,I Yokoyama,H.Inoko,H Takagi: "Significance of tumor necrosis factor microsatellite polymorphism in renal transplantation." Tissue Antigens. 50・5. 484-488 (1997)

[文献書誌] T Nagasaka,I Yokoyama,T Muramatsu,H Takagi: "α-Galactosyl oligosaccharides conjugated with polyethylene glycol as potential inhibitors of hyperacute rejection upon xenotransplantation" Biochemical and Biophysical Research Communications. 232. 731-736 (1997)

[文献書誌] Yasutomi M,Yokoyama I,Takagi H: "Evaluation of tetrahydropyranyladriamycin as an immunosuppressant in concordant xenotransplantation" The Journal of Heart Lung Transplantation. 16・8. 283-289 (1997)

[文献書誌] S Hayashi,I Yokoyama,H Takagi: "Protection of xeno-hepatocytes from complement-mediated cytolysis by transduction with homologous restriction factor 20 gene using retroviral vector." European Surgical Research. 30・3. 161-167 (1998)

[文献書誌] A Katayama,I Yokoyama,T Muramatsu,H Takagi: "Porcinr α-1.3-galactosyltransferase:full length cDNA cloning,genomic organization,and analysis of splicing variants" Glycoconjugate Journal. 15. 583-589 (1998)

[文献書誌] S.Hayashi,I Yokoyama,and H.Takagi: "Technique of Triple Splir-Liver Transplantation in Pigs Using Inferior Vena Cava Reconstruction and Intraoperative Intrahepatic Portosystemic Shunt" Transplantation Proceedings. 30・7. 3229-3231 (1998)

[文献書誌] S Hayashi,M.G.Lin,I Yokoyama,H Takagi: "Auxiliary orthotopic Xenogeneic Liver Transplantation Using Pigs for Fulminant Hepatic failure:With Special Reference to the Technique and Immunosuppression" Transplantation Proceedings. 30. 3836-3836 (1998)

[文献書誌] T.Nagasaka,I Yokoyama,and H.Takagi: "Inhibitory Effect of α(1,2)Fucosyltransferase Recombinant Adenoviral Vector on α Gal Expression" Transplantation Proceedings. 30. 3837-3838 (1998)

[文献書誌] 小川晴子、小林孝彰、門松健治、横山逸男、高木 弘、村松 喬: "異種移植における抗原の制御" Organ Biology. 5・4. 25-33 (1998)

[文献書誌] Shuji Hayashi,Takaharu,I Yokoyama Nagasaka,Taiki Kojima,Yasushi,Namii,Akio: "Combination splitting using both in situ and ex situ Techniques in triple split liver transplantation in pigs" Transplantation International. 11. 408-412 (1998)

1998 年度実績報告書

横山逸男名古屋大学, 医学部, 講師 (60240206)

[文献書誌] 林衆治、横山逸男、高木弘: "同種移植及び異種移植における遺伝子制御に関する研究" 今日の移植. 11・2. 157-164 (1997)

[文献書誌] 小川晴子、小林孝彰、門松健治、横山逸男、高木弘、村松喬: "異種移植における抗原の制御" Organ Biology. 5・4. 25-33 (1998)