2002 Fiscal Year Annual Research Report

自然免疫における生体防御レクチンの役割

Research Project

Project/Area Number	13143204
Research Institution	Fukushima Medical University
Principal Investigator	藤田禎三福島県立医科大学, 医学部, 教授 (20134223)
Co-Investigator(Kenkyū-buntansha)	中田宗宏東海大学, 工学部, 助教授 (00266371) 高橋実福島県立医科大学, 医学部, 助手 (00285024) 遠藤雄一福島県立医科大学, 医学部, 助教授 (20117427) 安住薫北海道大学, 薬学研究科, 助手 (90221720) 中村隆範香川医科大学, 医学部, 教授 (70183887)
Keywords	自然免疫 / 補体 / レクチン / MBL / MASP / フィコリン / 分子進化
Research Abstract	血清中に存在するマンノース結合レクチン(MBL)やフィコリンは自然免疫に働く生体防御レクチンである。本研究の目的は、生体防御レクチンの自然免疫における役割を明らかにするもので、本年度は以下の成果を得た。 1.イギリスのと共同研究で抗ガン剤の投与により、免疫力が低下している患者さんにおいてMBLとフィコリンの血中濃度を測定し、生体内での役割を推定した(投稿中)。また、マウスフィコリン欠損動物の作製に着手した。 2.当研究室で作製したMASP-1/3欠損マウス血清を用いて、補体レクチン経路の活性化機構について検討した。まず、蛋白としてのMASP-1とMASP-3が欠損していることを確認し、C4,C2を活性化するMASP-2の活性化におけるMASP-1の役割りを検討した。この結果、MASP-2はそれ自体で活性化を起こすが、MASP-1の存在下ではその効率が著しくよくなることが判明した(投稿準備中)。さらに、MASP-2遺伝子の欠落した遺伝子改変マウスを作製し、交配により両染色体に遺伝子変異を持つホモ型MASP-2欠損マウス欠損マウスの誕生を待つばかりである。 3.円口類のヤツメウナギにおいて2種類の新規なレクチンを発見し、その一つは、コラーゲン構造を持つMBLであり、興味深いことにもう一つのレクチンは、C1qであった。このことは、補体レクチン経路から古典的経路へ進化したことを示す。また、両生類のゼノパスにおいて4種類のフィコリンの遺伝子をクローニングし(Immunogenetics, in press)、MASPの分子進化について明らかにした(J.Immunol, in press)。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] Matsushita M et al.: "Activation of the lectin complement pathway by H-ficolin (Hakata antigen)"J.Immunol.. 168(7). 3502-3506 (2002)
[Publications] Fujita T: "Evolution of the lectin-complement pathway and its role in innate immanity"Nat.Rev.Immunal.. 2(5). 346-353 (2002)
[Publications] Endo Y et al.: "Functional Characterization of human mannose-binding lectin-associated serine protease (MASP)-9/3 and MASP-2 promoters, and comparison with the Cls"Int.Immunol.. 14(10). 1193-1201 (2002)
[Publications] Matsushita M, Fujita T: "The roles of ficolins in innate immunity"Immunobiology. 205(4-5). 490-497 (2002)
[Publications] Kuraya M et al.: "Expression of H-ficolin/Hakata antigen, mannose-binding lectin-associated serine protease (MASP)-1 and MASP-3 by human glioma"Int.Immunol.. 15(1). 109-117 (2003)
[Publications] Mukai K et al.: "HER2 peptide-specific CD8^+ T cells are proportionally detectable long after multiple DNA vaccinations"Gene Ther.. 9. 879-888 (2002)
[Publications] Hata H et al.: "Occurrence of tumor antigen pRLIa specific CD8 T cells in spleen cells from syngeneic BALB/c, semiallogeneic (BALB/c x C57BL/6)"Int.J.Oncol.. 20. 1019-1025 (2002)
[Publications] Kiso T et al.: "Enhanced expression of decay-accelerating factor and CD59/homologods restriction factor 20 in intestinal metaplasia, gastric adenomas"Histopathology. 40. 339-347 (2002)
[Publications] Kakinuma Y et al.: "Molecular cloning and characterization of novel ficolins from xenopus laevis"Immunogenet.. (in press). (2003)
[Publications] Endo Y et al.: "Origin of mannose-binding lectin-associated serine protease (MASP)-1 and MASP-3 involved in the lectin complement pathway"J.Immunol.. (in press). (2003)
[Publications] Shida K et al.: "Hemocytes of Ciona intestinalis express multiple genes involved in innate host defense"Biochem.Biophys.Res.Commun.. 302(2). 207-218 (2003)
[Publications] Dehal P et al.: "The draft genome of Ciona intestinalis : insights into chordate and vertebrate"Science. 298(5601). 2157-2167 (2002)
[Publications] Azumi K et al.: "Zymosan induces production of superoxide anions by hemocytes of the ascidian Halocynthia roretzi"Comp.Biochem.Physiol.C.Toxicol.Pharmacol.. 133(4). 567-574 (2002)
[Publications] Shoji H et al.: "Characterization of the Xenopus galectin family-Three structurally different types as in mammals and regulated expression during"J.Biol.Chem.. (in press). (2003)
[Publications] Asakura H et al.: "Selective eosinophil adhesion to fibroblast via IFN-gamma-induced galectin-9"J.Immunol.. 169(10). 5912-5918 (2002)
[Publications] Tang W et al.: "Association of histochemical expression of Maackia amurensis leukoaggutinin-positive glycoconjugates with behaviour of human"Histopathology. 42(3). 239-245 (2003)

2002 Fiscal Year Annual Research Report

自然免疫における生体防御レクチンの役割

Principal Investigator

藤田 禎三 福島県立医科大学, 医学部, 教授 (20134223)

Research Products

[Publications] Matsushita M et al.: "Activation of the lectin complement pathway by H-ficolin (Hakata antigen)"J.Immunol.. 168(7). 3502-3506 (2002)

[Publications] Fujita T: "Evolution of the lectin-complement pathway and its role in innate immanity"Nat.Rev.Immunal.. 2(5). 346-353 (2002)

[Publications] Endo Y et al.: "Functional Characterization of human mannose-binding lectin-associated serine protease (MASP)-9/3 and MASP-2 promoters, and comparison with the Cls"Int.Immunol.. 14(10). 1193-1201 (2002)

[Publications] Matsushita M, Fujita T: "The roles of ficolins in innate immunity"Immunobiology. 205(4-5). 490-497 (2002)

[Publications] Kuraya M et al.: "Expression of H-ficolin/Hakata antigen, mannose-binding lectin-associated serine protease (MASP)-1 and MASP-3 by human glioma"Int.Immunol.. 15(1). 109-117 (2003)

[Publications] Mukai K et al.: "HER2 peptide-specific CD8^+ T cells are proportionally detectable long after multiple DNA vaccinations"Gene Ther.. 9. 879-888 (2002)

[Publications] Hata H et al.: "Occurrence of tumor antigen pRLIa specific CD8 T cells in spleen cells from syngeneic BALB/c, semiallogeneic (BALB/c x C57BL/6)"Int.J.Oncol.. 20. 1019-1025 (2002)

[Publications] Kiso T et al.: "Enhanced expression of decay-accelerating factor and CD59/homologods restriction factor 20 in intestinal metaplasia, gastric adenomas"Histopathology. 40. 339-347 (2002)

[Publications] Kakinuma Y et al.: "Molecular cloning and characterization of novel ficolins from xenopus laevis"Immunogenet.. (in press). (2003)

[Publications] Endo Y et al.: "Origin of mannose-binding lectin-associated serine protease (MASP)-1 and MASP-3 involved in the lectin complement pathway"J.Immunol.. (in press). (2003)

[Publications] Shida K et al.: "Hemocytes of Ciona intestinalis express multiple genes involved in innate host defense"Biochem.Biophys.Res.Commun.. 302(2). 207-218 (2003)

[Publications] Dehal P et al.: "The draft genome of Ciona intestinalis : insights into chordate and vertebrate"Science. 298(5601). 2157-2167 (2002)

[Publications] Azumi K et al.: "Zymosan induces production of superoxide anions by hemocytes of the ascidian Halocynthia roretzi"Comp.Biochem.Physiol.C.Toxicol.Pharmacol.. 133(4). 567-574 (2002)

[Publications] Shoji H et al.: "Characterization of the Xenopus galectin family-Three structurally different types as in mammals and regulated expression during"J.Biol.Chem.. (in press). (2003)

[Publications] Asakura H et al.: "Selective eosinophil adhesion to fibroblast via IFN-gamma-induced galectin-9"J.Immunol.. 169(10). 5912-5918 (2002)

[Publications] Tang W et al.: "Association of histochemical expression of Maackia amurensis leukoaggutinin-positive glycoconjugates with behaviour of human"Histopathology. 42(3). 239-245 (2003)

藤田禎三福島県立医科大学, 医学部, 教授 (20134223)