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Chemical-induced hypersensitivity, cellular mechanism and its regulation

Research Project

Project/Area Number 16390033
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionThe University of Tokyo

Principal Investigator

NOBUAKI Higashi  The University of Tokyo, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学系研究科, 助教授 (40302616)

Co-Investigator(Kenkyū-buntansha) TATSURO Irimura  The University of Tokyo, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学系研究科, 教授 (80092146)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2005: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2004: ¥6,900,000 (Direct Cost: ¥6,900,000)
Keywordschemical-induced hypersensitivity / macrophages / dendritic cells / lymph nodes / lectin / skin inflammation / allergy / hapten / 抗原提示 / サイトカイン
Research Abstract

Aim of the present research is to analyze cellular responses of mice that are treated with low molecular chemicals or haptens. We focus on cell surface antigens, cell behavior, migration, and physiological relevance of a subpopulation of skin macrophage/dendritic-lineage cells that are identified with cell surface expression of macrophage galactose-type C-type lectins 1/2 (MGL1/2).
Our main efforts are summarized on the following four points. (1)Migration of MGL1/2-positive cells from skin to draining lymph nodes was immunohistochemically confirmed. MGL1+MGL2+ cells in the lymph node were identified as dermal dendritic cells that carry hapten and are distinct from Langerhans cells. Another MGL+ cells (MGL1+MGL2-)were plasmacytoid dendtiric cells. (2)Sialoadhesin was identified as a counterreceptor of MGL1 that regulates migratory property of MGL1/2-positive cells from skin to draining lymph nodes. Another three candidates as MGL1- binding proteins were successfully detected and isolated in SDS-PAGE. (3)Crucial roles of MGL1 in contact hypersensitivity and antigen-induced granulation tissue formation were experimentally demonstrated using mouse disease models. During antigen-induced granulation tissue formation, the MGL1/2-positive cells produced inflammatory cytokines such as IL-1a and thus induced extracellular matrix synthesis in the tissue. (4)Mice deficient of MGL-1 expression or those injected with anti-MGL1 antibody (LOM-8.7)showed suppressed tissue formation during the antigen-dependent disease model. The effort (4)suggests that compounds that inhibit MGL-dependent binding are potentially utilized for anti-inflammatory drugs that can suppress migration or activation of MGL1/2-positive cells.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (27 results)

All 2006 2005 2004

All Journal Article (27 results)

  • [Journal Article] マクロファージの浸潤におけるヘパラナーゼの活性調節機構 : 接着に伴う酵素の集積は活性を制御するか?2006

    • Author(s)
      東 伸昭, 入村達郎, 中島元夫
    • Journal Title

      生化学 78.1

      Pages: 34-38

    • NAID

      10017148516

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulatory mechanisms for heparanase activity during macrophage migration.2006

    • Author(s)
      Higashi N, Irimura T, Nakajima M.
    • Journal Title

      Seikagaku 78(1)

      Pages: 34-38

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] マクロファージの浸潤におけるヘパラナーゼの活性調節機構:接着に伴う酵素の集積は活性を制御するか?2006

    • Author(s)
      東 伸昭, 入村達郎, 中島元夫
    • Journal Title

      生化学 78・1

      Pages: 34-38

    • NAID

      10017148516

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Granulation tissue formation by nonspecific inflammatory agent occurs independently of macrophage galactose-type C-type lectin-1.2005

    • Author(s)
      Sato K, Higashi N, Irimura T et al.
    • Journal Title

      Clin. Immunol. 115

      Pages: 47-50

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Redistributions of macrophages expressing the macrophage galactose-type C-type lectin (MGL) during antigen-induced chronic granulation tissue formation.2005

    • Author(s)
      Sato K, Higashi N, Irimura T et al.
    • Journal Title

      Int. Immunol. 17

      Pages: 559-568

    • NAID

      10019359300

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Lack of antigen-specific tissue remodeling in mice deficient in the macrophage galactose-type calcium-type lectin 1/CD301a.2005

    • Author(s)
      Sato K, Higashi N, Irimura T et al.
    • Journal Title

      Blood 106

      Pages: 207-215

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Distribution of MGL1 binding sites and MGL1/2-pisitive cells in lymph nodes during the sensitization phase of contact hypersensitivity.2005

    • Author(s)
      Sato K, Higashi N, Kumamoto Y, Irimura T
    • Journal Title

      Acta Histochem. Cytochem. 38

      Pages: 75-80

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Granulation tissue formation by nonspecific inflammatory agent occurs independently of macrophage galactose-type C-type lectin-1.2005

    • Author(s)
      Sato K, Komatsu N, Higashi N, Imai Y, Irimura T.
    • Journal Title

      Clin Immunol 115

      Pages: 47-50

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Redistributions of macrophages expressing the macrophage galactose-type C-type lectin (MGL) during antigen-induced chronic granulation tissue formation.2005

    • Author(s)
      Sato K, Imai Y, Higashi N, Kumamoto Y, Mukaida N, Irimura T.
    • Journal Title

      Int Immunol 17

      Pages: 559-568

    • NAID

      10019359300

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Lack of antigen-specific tissue remodeling in mice deficient in the macrophage galactose-type calcium-type lectin 1 /CD301a.2005

    • Author(s)
      Sato K, Imai Y, Higashi N, Kumamoto Y, Onami TM, Hedrick SM, Irimura T.
    • Journal Title

      Blood 106

      Pages: 207-215

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Distribution of MGL1 binding sites and MGL1/2- positive cells in lymph nodes during the sensitization phase of contact hypersensitivity.2005

    • Author(s)
      Sato K, Higashi N, Kumamoto Y, Irimura T.
    • Journal Title

      Acta Histochem Cytochem 38

      Pages: 75-80

    • NAID

      110003161232

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Granulation tissue formation by nonspecific inflammatory agent occurs independently of macrophage galactose-type C-type lectin-1.2005

    • Author(s)
      Sato K, Komatsu N, Higashi N, Imai Y, Irimura T
    • Journal Title

      Clin.Immunol. 115

      Pages: 47-50

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Redistributions of macrophages expressing the macrophage galactose-typeC-type lectin (MGL) during antigen-induced chronic granulation tissue formation.2005

    • Author(s)
      Sato K, Imai Y, Higashi N, Kumamoto Y, Mukaida N, Irimura T
    • Journal Title

      Int.Immunol. 17

      Pages: 559-568

    • NAID

      10019359300

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Lack of antigen-specific tissue remodeling in mice deficient in the macrophage galactose-type calcium-type lectin 1/CD301a.2005

    • Author(s)
      Sato K, Imai Y, Higashi N, Kumamoto Y, Onami TM, Hedrick SM, Irimura T
    • Journal Title

      Blood 106

      Pages: 207-215

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Distribution of MGL1 binding sites and MGL1/2-positivee cells in lymph nodes during the sensitization phase of contact hypersensitivity.2005

    • Author(s)
      Sato K, Higashi N, Kumamoto Y, Irimura T
    • Journal Title

      Acta Histochem.Cytochem. 38

      Pages: 75-80

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Redistribution of macrophages expressing the macrophage galactose-type C-type lectin (MGL) during antigen-induced chronic granulation tissue formation2005

    • Author(s)
      Sato, Imai, Higashi et al.
    • Journal Title

      Int.Immunol. (in press)

    • NAID

      10019359300

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Distribution of MGL1 binding sites and MGL1/2-positive cells in lymph nodes during the sensitization phase of contact hypersensitivity2005

    • Author(s)
      Sato, Higashi et al.
    • Journal Title

      Acta Histochem.Cytochem. (in press)

    • NAID

      110003161232

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Granulation Tissue Formation by Nonspecific Inflammatory Agent Occurs Independently of Macrophage Galactose-type C-type Lectin-12005

    • Author(s)
      Sato, Komatsu et al.
    • Journal Title

      Clin.Immunol. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of sialoadhesin as a dominant lymph node counter-receptor for mouse macrophage galactose-type C-type lectin 1.2004

    • Author(s)
      Kumamoto Y., Higashi N., Irimura T et al.
    • Journal Title

      J. Biol. Chem. 279

      Pages: 49274-49280

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry.2004

    • Author(s)
      Sasaki N, Higashi N, Irimura T et al.
    • Journal Title

      J. Virol. 78

      Pages: 2943-2947

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry.2004

    • Author(s)
      Takada Y, Higashi N, Irimura T et al.
    • Journal Title

      J. Virol. 78

      Pages: 2943-2947

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification of sialoadhesin as a dominant lymph node counter-receptor for mouse macrophage galactose-type C-type lectin 1.2004

    • Author(s)
      Kumamoto Y, Higashi N, Denda-Nagai K, Tsuiji M, Sato K, Crocker PR, Irimura T.
    • Journal Title

      J Biol Chem 279

      Pages: 49274-49280

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cell surface localization of heparanase on macrophages regulates degradation of extracellular matrix heparan sulfate.2004

    • Author(s)
      Sasaki N, Higashi N, Taka T, Nakajima M, Irimura T.
    • Journal Title

      J Immunol 172

      Pages: 3830-3835

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry.2004

    • Author(s)
      Takada A, Fujioka K, Tsuiji M, Morikawa A, Higashi N, Ebihara H, Kobasa D, Feldmann H, Irimura T, Kawaoka Y.
    • Journal Title

      J Virol 78

      Pages: 2943-2947

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cell surface localization of heparanase on macrophages regulates degradation of extracellular matrix heparan sulfate2004

    • Author(s)
      Sasaki, Higashi et al.
    • Journal Title

      J.Immunol. 172・6

      Pages: 3830-3835

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry2004

    • Author(s)
      Takada, Fujioka et al.
    • Journal Title

      J.Virology 78・6

      Pages: 2943-2947

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of sialoadhesin as a dominant lymph node counter-receptor for mouse macrophage galactose-type C-type lectin 12004

    • Author(s)
      Kumamoto, Higashi et al.
    • Journal Title

      J.Biol.Chem. 279・47

      Pages: 49274-49280

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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