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Studies on effector molecules of innate immunity responsible for cytotoxicity to tumor cells.

Research Project

Project/Area Number 10470478
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

NAGASAWA Shigeharu  Hokkaido Univ.Grad.Sch.Pharm.Sci., Pro., 大学院・薬学研究科, 教授 (70029958)

Co-Investigator(Kenkyū-buntansha) MURAKAMI Yusuke  Hokkaido Univ.Grad.Sch.Pharm.Sci., Inst., 大学院・薬学研究科, 助手 (10250466)
YAMASHITA Toshiyuki  Hokkaido Univ.Grad.Sch.Pharm.Sci., Lec., 大学院・薬学研究科, 講師 (90192400)
TAKAHASHI Kazuhiko  Hokkaido Univ.Grad.Sch.Pharm.Sci., Asso.Pro., 大学院・薬学研究科, 助教授 (10113581)
SEYA Tsukasa  Osaka Med.Cent.Cancer and Cardiovas.Diseases, Div.Head., 部長 (10301805)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2000: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1998: ¥7,400,000 (Direct Cost: ¥7,400,000)
Keywordssulfatides / neutrophils / tumor cells / phagocytosis / complement / M.fermentans / apoptosis / EF-1α / セレブロシド / 補体 / スフィンゴ脂質
Research Abstract

A.Enhancement of CR3-mediated neutrophil phagocytosis by sulfatides.
Sulfatides is a ligand for L-selectin and triggers intracellular signals in human neutrophils. We found for the first time the enhancement of CR3-mediated human neutrophil phagocytosis by sulfatides. FcR-mediated phagocytosis was not modified by sulfatides treatment We also observed that unidentified receptor for sulfatides exists on human neutrophils and participates in the enhancement of phagocytosis.
B.Homologous complement activators expressed on apoptotic and malignant cells.
a ; Apoptotic as well as native T cells were found to contain a homologous complement activator of 50 kDa. Amino acid seqenece analysis was identical to those of elongation factor 1α. The homologous complement activator activity was removed with anti-EF-1α.
b. We found a M161Ag, which is expressed on human malignant cells and induces homologous complement activation. cDNA of M161Ag revealed that it is highly homologous to P48, mycoplasma fermentans gene product. It was revealed that latently infected M.fermentans allows human cells to produce M161Ag, which is a potent modulator of innate and cellular immune responses via its complement activating and cytokine-producing activity.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Sakai,M., et al.: "Enhancement of FcgR-and CR3-mediated neutrophil phagocytosis by cerebrosides."Biochem.Biophys.Res.Communs.. 278. 79-83 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aoki,H., et al.: "Elongation factor-1a as a homologous complement activator of Jurkat cells."Int.J.Mol.Med.. 6. 87-92 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Begum,N.A., et al.: "Molecular remodeling of human CD46 for xenotransplantation ; designing a potent complement regulator without measles virus receptor activity."Immunology. 100. 131-139 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murakami,Y., et al.: "Effect of mutations at the residues R25,D27,P69 and N70 of B95a-MCP on receptor activities for the measles viruses Nagahata wild-type strain and CAM vaccine strain."Inter.J.Molec.Med.. 3. 25-32 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsumoto,M., et al.: "Structural and functional properties of complement-activating protein M161Ag, a mycoplasma fermentans gene product that induces cytokine production by human monocytes"J.Biol.Chem.. 273. 12407-12414 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Seya,T., et al.: "CD46 (membrane cofactor protein of complement, measles virus receptor) : structural and functional divergence among species (Review)"Inter.J.Mol.Med.. 1. 809-816 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakai, M., Nagasawa, S., & Takahashi, K.: "Enhancement of FcgR- and CR3-mediated neutrophil phagocytosis by cerebrosides."Biochem.Biophys.Res.Communs.. 278. 79-83 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aoki, H., Takizawa, F., Tsuji, S., & Nagasawa, S.: "Elongation factor-1α as a homologous complement activator of Jurkat cells."Int.J.Mol.Med.. 6. 87-92 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Begum, N.A., Murakami, Y., Matsumoto, M., Hatanaka, M., Nagasawa, S., Kinoshita, T., & Seya, T.: "Molecular remodeling of human CD46 for xenotransplantation ; designing a potent complement regulator without measles virus receptor activity."Immunology. 99. 1-13 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murakami, Y., Fukui, A., Seya, T., Ueda, S., & Nagasawa, S.: "Effect of mutations at the residues R25, D27, P69 and N70 of B95a-MCP on receptor activities for the measles viruses Nagahata wild-type strain and CAM vaccine strain."Inter.J.Molec.Med.. 3. 25-32 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Seya, T., Nomura, M., Murakami, Y., Begum, N.A., Matsumoto, M., & Nagasawa, S.: "CD46 (membrane cofactor protein of complement, measles virus receptor) : structural and functional divergence among species (Review)""Inter.J.Mol.Med.. 1. 809-816 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mikata, S., Miyagawa, S., Fukui, A., Murakami, Y., Shirakura, R., Matsuda, H., Hatanaka, M., Matsumoto, M., Seya, T., Suzuki, K., & Nagasawa, S.: "A monomeric human C4b-binding protein (C4bp) more efficiently inactivates C3b than natural C4bp ; participation of C-terminal domains in factor l-cofactor activity."Molec.Immunol.. 35. 537-544 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsumoto, M., Nishiguchi, M., Kikkawa, S., Nishimura, H., Nagasawa, S., and Seya, T.: "Structural and functional properties of complement-activating protein M161Ag, a micoplasma fermentans gene product that induces cytokine production by human monocytes."J.Biol.Chem.. 273. 12407-12414 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hara, T., Matsumoto, M., Tsuji, S., Nagasawa, S., and Seya, T.: "Homologous complement activation on drug-induced apoptotic cells from human adenocarcinoma cell line."Immunobiol.. 196. 491-503 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakai, M.et.al: "Enhancement of FcrR- and CR3-mediated neutrophil phagocytosis by cerebrosides. "Biochem. Biophys.Res.Communs.. 278. 79-83 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Aoki, H.et al.: "Elongation factor 1-a as a homologous complement activator of Jurkat cells."Int.J.Mol.Med.. 6. 87-92 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Begum, N.A.et.al: "Molecular remodelling of human CD46 for xenotransplantation : designing a potent complement regulator without measles virus receptor activity."Immunology. 100. 131-139 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Murakami, Y.et.al: "Effect of mutations at the residues R25, D27, P69, and N70 of B95a-MCP on receptor activities for the measles viruses Nagahata wild-type strain"Int.J.Mol.Med.. 3. 25-32 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Murakami, Y.: "Effect of mutations at the residues R25, D27, P69 and N70 of B95a-MCP on receptor activities for the measles viruses strain"Inter. J. Molec. Med.. 3. 25-32 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akazawa, T.: "A novel negative regulator molecule, Cho-1, is involved in the cytotoxicity by human natural killer cells but not in cytotoxic t lymphocytes"Microbiol. Immunol.. 43. 285-291 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nanbo, A.: "Lipopolysaccharide stimulates Hep G2 human hepatoma cells in the presence of lipopolysaccharide-binding protein via CD14"Eur. J. Biochem. 260. 183-191 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Seya, T.: "Molecular remodeling of complement regulatory proteins for xenoplantation"Immunopharmacology. 42. 75-80 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yusuke Murakami,et al.: "Molecular cloning of membrane cofactor protein(MCP)on B95a cell,an Epstein-Barr virus-transformed marmoset B cell line" Biochem.J.330. 1351-1359 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsukasa Seya et al.: "CD46(membrane cofactor protein of complement,measles virus receptor);structural and functional devergence among species." Int.J.Molec.Med.1. 809-816 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yusuke Murakami et al.: "Effect of mutations at the residues R25,D27,P69,and N70 of B95a-MCP on receptor activities for MV" Int.J.Molec.Med.3. 25-32 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shoki Mikata et al.: "A monomeric human C46-binding protein(C4bp)more efficiently inactivates C3b than natural C4bp;participation of C-terminal domains." Molec.Immunol.35. 537-544 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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