1998 Fiscal Year Annual Research Report

麻疹ウィルスによる宿主免疫抑制の分子機構

Research Project

Project/Area Number	10470083
Research Category	Grant-in-Aid for Scientific Research (B)
Research Institution	Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses
Principal Investigator	瀬谷司大阪府立成人病センター研究所, 第6部, 部長 (10301805)
Co-Investigator(Kenkyū-buntansha)	枦木修広島大学, 医学部・総合薬学学科, 教授 (80142751) 松本美佐子大阪府立成人病センター研究所, 第6部, 主任研究員
Keywords	麻疹ウィルス / 免疫抑制 / innate immunity(基本免疫) / 抗原提示細胞 / IL-12 / ホスファターゼ / 補体
Research Abstract	CD46のCYTにはVXYXXLのホスファターゼ結合部位/エンドソーム標的シグナルがある。CD46とSHP-1のassociationをヒトマクロファージ(GM-CSF誘導)の分化過程で追跡した。SHP-1は培養6日目、単球がマクロファージ活性化する際にCD46にリクルートされることが判明した。SHP-1は麻疹ウィルス(MV)によって一過性に解離する。リン酸化蛋白質はまだ同定されていない。anti-PYによるプローブとin vitro kinase assyを予定している。この際、ウィルス株の中にはIL-12を強力にinduceするものがあった。報告のようなIL-12の産生抑制は見られなかった。 CD46はnegative receptorの特徴をもつこととSHP-1のリクルートメントの関係を今後明らかにしていきたい。さらにマクロファージのCD46をnatural ligands(補体C3b)や抗体でcross-linkして、MVの結果を裏づけていく予定である。またRRKKKのERMfamily結合部位/ER標的シグナルについてCD46の免疫沈降でcomplexを確認中である。これらとsignaltransductionとの関連を免疫担当細胞で明らかにしていく予定である。 Innate immune system(APC,macrophages)がウィルスの初期targetであることは証明できるが、innate immune systemとウィルス感染の関連はまだ未解明の問題が手付かずのまま残されている。

Research Products
(19 results)

All Other

All Publications (19 results)

[Publications] Mikata,S.: "Regulation of human complement-mediated swine endolhelial cell lysis by surface-bound form of human C46-binding protein" Transplantation. 65. 363-368 (1998)
[Publications] Hatanaka,M.: "Homodimerization of a GPI-anchored complement regulatory protein CD59 on the surface of Hela and CD59-transfected CHO cells" J.Biochem.123. 579-586 (1998)
[Publications] Hara,T.: "Post-translational modification and intracellular localization of a splice product of CD46 cloned from the human testis:Ro of the intracellulardomc in O-glycosylatic" Immunology. 93. 546-555 (1998)
[Publications] Mikata,S.: "New approach to prevent complement activation on xenografts effects of a surface-bound form of human C46-binding protein" Transplant.Proc.30. 65-66 (1998)
[Publications] Matsumoto,M.: "Structural and functional properlies of complement-activating protein M161Ag.a Mycoplasma fermentans gene product that induces cytoki production by human monocytes." J.Biol.Chem.273. 12407-12414 (1998)
[Publications] Sakata,H.: "A Japanese wild-type measles virus strain inducing predominant early down-rgulation of CD46." Biol.Pharmac.Bull.21. 1121-1127 (1998)
[Publications] Kurita,M.: "Antibody-independent classical complement pathway activation and homologous C3 deposition on human xeroderma cell lines." Clin.Exp.Immunol. (in press). (1999)
[Publications] Seya,T.: "Innate immune therapy for cancer:lessons from M161Ag,a mycoplasma product" Human Gene Therapy ed.by N.Habib IBC press,UK pp. (in press). (1999)
[Publications] Murakami,Y.: "Effect of mutations at the residues R25,D27,P69,and N70 of B95a・MCD on receptor activities for the measles viruses Nagahata wild-type strain and CA Myvaccine strain." Int.J.Mol.Med.3. 25-32 (1999)
[Publications] Matsumoto,M.: "M161Ag is a potent cytokine inducer with complement activating function (Review)" Int.J.Molec.Med.3. 291-295 (1999)
[Publications] Seya,T.: "Molecular remodeling of complement regulatory proteins for xenotransplantation." Immunopharmacology. (in press). (1999)
[Publications] Seya,T.: "Innate immune therapy for cancer:seeking fon effective molecules for activation of the innate immune system." Human Grne Therapy ed.by N.Habib,Plenum press,USA pp. (in press). (1999)
[Publications] Seya,T.: "CD46 (membrane cofactor protein (MCP) of complement,measles virus receptor):structurland functional divergence among species(Review)." Int.J.Molec.Med.21. 1121-1127 (1998)
[Publications] Mikata,S.: "Amonomeric human C4b-binding protein (C46p) move efficiently inactivates C3b than natural C4bp:Participation of C・terminal domains in factor I-cotactor activic" Molec.Immunol.35. 537-544 (1998)
[Publications] Saeki,Y.: "Phosphatidylinositol 3 kinase inhibitors block matrix adhesion and experimental metastasis of high metastatic mouse hepatoma clone" J.Biochem. 124. 1020-1025 (1998)
[Publications] Begum,N.A.: "ABCG-CWS-regulated gene in human monocytes by differential display Identification of a human homologue of chicken MD-1" Biolchem.Biophys.Res.Commun.(in press). (1999)
[Publications] Hatanaka,M.: "Expression of caveolin-1 in human T cell leukemia cell lines." Biolchem.Biophys.Res.Commun.253. 382-387 (1998)
[Publications] Kawano,M.: "Elevated serum levels of soluble membrane cofactor protein (CD46,MCP) in patients with systemic lupus erythematosis" Clin.Exp.Immunol.(in press). (1999)
[Publications] Seya,T.: "Human membrane cofactor protein of complement (CD46): multiple isoforms and functions." Int.J.Biochem.Cell Biol.(in press). (1999)

1998 Fiscal Year Annual Research Report

麻疹ウィルスによる宿主免疫抑制の分子機構

Principal Investigator

瀬谷 司 大阪府立成人病センター研究所, 第6部, 部長 (10301805)

Research Products

[Publications] Mikata,S.: "Regulation of human complement-mediated swine endolhelial cell lysis by surface-bound form of human C46-binding protein" Transplantation. 65. 363-368 (1998)

[Publications] Hatanaka,M.: "Homodimerization of a GPI-anchored complement regulatory protein CD59 on the surface of Hela and CD59-transfected CHO cells" J.Biochem.123. 579-586 (1998)

[Publications] Hara,T.: "Post-translational modification and intracellular localization of a splice product of CD46 cloned from the human testis:Ro of the intracellulardomc in O-glycosylatic" Immunology. 93. 546-555 (1998)

[Publications] Mikata,S.: "New approach to prevent complement activation on xenografts effects of a surface-bound form of human C46-binding protein" Transplant.Proc.30. 65-66 (1998)

[Publications] Matsumoto,M.: "Structural and functional properlies of complement-activating protein M161Ag.a Mycoplasma fermentans gene product that induces cytoki production by human monocytes." J.Biol.Chem.273. 12407-12414 (1998)

[Publications] Sakata,H.: "A Japanese wild-type measles virus strain inducing predominant early down-rgulation of CD46." Biol.Pharmac.Bull.21. 1121-1127 (1998)

[Publications] Kurita,M.: "Antibody-independent classical complement pathway activation and homologous C3 deposition on human xeroderma cell lines." Clin.Exp.Immunol. (in press). (1999)

[Publications] Seya,T.: "Innate immune therapy for cancer:lessons from M161Ag,a mycoplasma product" Human Gene Therapy ed.by N.Habib IBC press,UK pp. (in press). (1999)

[Publications] Murakami,Y.: "Effect of mutations at the residues R25,D27,P69,and N70 of B95a・MCD on receptor activities for the measles viruses Nagahata wild-type strain and CA Myvaccine strain." Int.J.Mol.Med.3. 25-32 (1999)

[Publications] Matsumoto,M.: "M161Ag is a potent cytokine inducer with complement activating function (Review)" Int.J.Molec.Med.3. 291-295 (1999)

[Publications] Seya,T.: "Molecular remodeling of complement regulatory proteins for xenotransplantation." Immunopharmacology. (in press). (1999)

[Publications] Seya,T.: "Innate immune therapy for cancer:seeking fon effective molecules for activation of the innate immune system." Human Grne Therapy ed.by N.Habib,Plenum press,USA pp. (in press). (1999)

[Publications] Seya,T.: "CD46 (membrane cofactor protein (MCP) of complement,measles virus receptor):structurland functional divergence among species(Review)." Int.J.Molec.Med.21. 1121-1127 (1998)

[Publications] Mikata,S.: "Amonomeric human C4b-binding protein (C46p) move efficiently inactivates C3b than natural C4bp:Participation of C・terminal domains in factor I-cotactor activic" Molec.Immunol.35. 537-544 (1998)

[Publications] Saeki,Y.: "Phosphatidylinositol 3 kinase inhibitors block matrix adhesion and experimental metastasis of high metastatic mouse hepatoma clone" J.Biochem. 124. 1020-1025 (1998)

[Publications] Begum,N.A.: "ABCG-CWS-regulated gene in human monocytes by differential display Identification of a human homologue of chicken MD-1" Biolchem.Biophys.Res.Commun.(in press). (1999)

[Publications] Hatanaka,M.: "Expression of caveolin-1 in human T cell leukemia cell lines." Biolchem.Biophys.Res.Commun.253. 382-387 (1998)

[Publications] Kawano,M.: "Elevated serum levels of soluble membrane cofactor protein (CD46,MCP) in patients with systemic lupus erythematosis" Clin.Exp.Immunol.(in press). (1999)

[Publications] Seya,T.: "Human membrane cofactor protein of complement (CD46): multiple isoforms and functions." Int.J.Biochem.Cell Biol.(in press). (1999)

瀬谷司大阪府立成人病センター研究所, 第6部, 部長 (10301805)