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Studies on the molecular mechanisms by which phagocytes recognize and eliminate antigens

Research Project

Project/Area Number 62480419
Research Category

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

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionHokkaido University,

Principal Investigator

KOYAMA Jiro  Hokkaido Univ. Faculty of Pharm. Sci., 薬学部, 教授 (10025679)

Co-Investigator(Kenkyū-buntansha) YAMASHITA Toshiyuki  Hokkaido Univ. Faculty of Pharm. Sci., 薬学部, 助手 (90192400)
TAKAHASHI Kazuhiko  Hokkaido Univ. Faculty of Pharm. Sci., 薬学部, 助手 (10113581)
中村 亨  北海道大学, 薬学部, 助手 (30001978)
Project Period (FY) 1987 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1987: ¥5,100,000 (Direct Cost: ¥5,100,000)
KeywordsMacrophage / Polymorphonuclear leukocyte / Phagocytosis / Antibody / Fc receptor / NADPH oxidase / Phospholipase A_2 / ミクロフィラメント / スーパーオキシド
Research Abstract

The molecular mechanisms by which phagocytes can recognize and eliminate antigen was studied with guinea pig macrophages and polymorphonuclear leukocytes. The main results obtained are as follows.
1. Both macrophages and leukocytes possess two distinct Fc receptors: FcR_2 for IgG2, and FcR_<1,2> for IgG2 and IgG1.
2. In the binding and ingestion of sensitized erythrocytes by macrophages, FcR_2 was found to function more effectively than FcR_<1,2>. On the contrary, the phagocytosis of immune complexes of protein antigens was similarly mediated by FcR_2 and FcR_<1,2>, but FcR_<1,2> operated predominantly in the reaction, probably due to its larger number than FcR_2. Furthermore, the phagocytosis mediated by FcR_2 ceased within 3 hr, though that by FcR_<1,2> continued at least up to 8 hr. These results indicate that the relative functions of FcR_2 and FcR_<1,2> vary, dependently on the sort of antigen used.
3. FcR_2 on PMN was found to trigger the activation of the respiratory burst NADPH oxidase and phospholipase A_2, but FcR_<1,2> did scarcely so. On the contrary, FcR_<1,2> induced more rapidly and intensively the actin polymerization than FcR_2. FcR_2 and FcR_<1,2>, thus, seem to differ from each other in the mechanism by which they transmit their signal for triggering these responses of PMN.
4. When stimulated with immune complex or C5a, human leukocytes undergo an increase in the concentration of intracellular Ca^<2+> and O^-_ generation. The treatment of cells with pertussis toxin inhibited these responses to C5a, but not those to immune complex, indicating that a different sequence of reactions is involved by immune complex and C5a.
5. The evidence supporting that the NADPH oxidase is composed of the NADPH-cytochrome c reductase and cytochrome b<@2559<@D2 was obtained by reconstitution of the oxidase activity by the purified reductase and cytochrome b<@D2559<@D2.

Report

(3 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Masaki Sato: FEBS Letters. 224. 29-32 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Fumio Sakane: Biochemical and Biophysical Research Communications. 147. 71-77 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tohoru Nakamura: Journal of Biochemistry. 104. 383-387 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Masaki Sato: Molecular Immunology. 25. 205-211 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Manabu Shirato: FEBS Letters. 234. 231-234 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hideki Sato: Molecular Immunology. 26. 309-317 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Masaki Sato: "Different abilities of two distinct Fc receptors on guinea-pig polymorphonuclear leukocytes to trigger the arachidonic acid metabolic cascade." FEBS Letters. 224. 29-32 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Fumio Sakane: "Porcine polymorphonuclear leukocyte NADPH-cytochrome c reductase generates superoxide in the presence of cytochrome b_<559> and phospholipid." Biochemical and Biophysical Research Communications. 147. 71-77 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tohoru Nakamura: "The different roles of two distinct Fc receptors on guinea pig macrophages in the phagocytosis of sensitized sheep erythrocytes." Journal of Biochemistry. 104. 383-387 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Masaki Sato: "Two distinct Fc receptors on guinea-pig polymorphonuclear leukocytes differ from each other in their eliciting activities for O^-_ generation." Molecular Immunology. 25. 205-211 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Manabu Shirato: "Different sensitivities of the responses of human neutrophils stimulated with immune complex and C5a anaphylatoxin to pertussis toxin." FEBS Letters. 234. 231-234 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hideki Sato: "Relative abilities of two Fc receptors on guinea-pig macrophages to operate in the phagocytosis of soluble immune complexes." Molecular Immunology. 26. 309-317 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Tohoru,Nakamura: Journal of Biochemistry. 104. 383-387 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Masaki,Sato: Molecular Immunology. 25. 205-211 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Manabu,Shirato: FEBS Letters. 234. 231-234 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Hideki,Sato: Molecular Immunology. 26. 309-317 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Fumio Sakane: Biochemical and Biophysical Research Communications. 147. 71-77 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Hiroyuki Kojima: Journal of Biochemistry. 102. 1083-1088 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Masaki Sato: FEBS Letters. 224. 29-32 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Masaki Sato: Molecular Immunology. 25. 205-211 (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Toshiyuki Yamashita: Microbiology and Immunology. 32. 187-198 (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Toshiyuki Yamashita: Microbiology and Immunology. 32. 199-210 (1988)

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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