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Proteomics analysis of plasma protein complex regulating leukocyte interaction.

Research Project

Project/Area Number 15590228
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionOKAYAMA UNIVERSITY

Principal Investigator

NISHIBORI Masahiro  Okayama Univ, Grad Sch of Med and Dent, Prof., 大学院・医歯学総合研究科, 教授 (50135943)

Co-Investigator(Kenkyū-buntansha) MORI Shuji  Okayama Univ, Grad Sch of Med and Dent, Associate Prof., 大学院・医歯学総合研究科, 助教授 (50220009)
TAKAHASHI Hideo  Okayama Univ, Grad Sch of Med and Dent, Res.Assis., 大学院・医歯学総合研究科, 助手 (60335627)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsleukocyte / adhesion molecule / interaction / plasma protein / complex / cytokine / sepsis / polymyxin
Research Abstract

Sepsis and septic shock, often associated with multiple organ failure, still remain important causes of morbidity and mortality in intensive care units. Many types of therapeutic trials for the treatment of septic shock have failed. Lipopolysaccharide(LPS) is one of the major causes of septic shock. The polymyxin B-immobilized filter column (PMX) was developed for the adsorption of endotoxin by direct hemoperfusion and has been used for the treatment of LPS-induced septic shock. In this study, we demonstrated that PMX also specifically bound monocytes from the peripheral blood leukocytes of septic patients by the analysis of bound cells using immunocytochemical and electron microscopic techniques. The specific removal of monocytes from septic patients may produce beneficial effects by reducing the interaction between activated monocytes and functionally associated cells including vascular endothelial cells. We also investigated the humoral factors adsorbed on the PMX and identified the … More some of the proteins by amino acid sequencing of the purified proteins and Western blotting. These included cytokine-like proteins and macrophage migration inhibitory factor. PMX may exert beneficial effects through the adsorption of plural factors, LPS, monocytes and humoral factors in the treatment of septic shock. We also report the plural mechanisms for controlling the activity of monocytes by the regulation of the expression of adhesion molecules.
Sepsis and septic shock, often associated with multiple organ failure, still remain important causes of morbidity and mortality in intensive care units. Many types of therapeutic trials for the treatment of septic shock have failed, however, recent phase III studies using recombinant activated protein C demonstrated the effectiveness of this therapy.^<1,2> Lipopolysaccharide(LPS), one of the major causes of septic shock, together with LPS binding protein binds to CD14 on the surface of monocytes/macrophages, leading to the activation of signaling molecule complex of Toll-like receptor-4 (TLR-4) and MD2. Polymyxin B can bind LPS and neutralize its biological activity, therefore, the polymyxin B-immobilized filter (PMX) column was developed for the adsorption of endotoxin by hemoperfusion.^3 There is now increasing evidence supporting the usefulness of this treatment, showing improvement of survival rate in LPS-induced circulatory disorders and systemic inflammatory response syndrome. Moreover, the effectiveness of hemoperfusion with this column for septic shock beyond LPS endotoxemia^4 prompted us to investigate additional mechanisms. Since it is well known that different populations of leukocytes are activated during septic shock and change their adhesive phenotype, we hypothesized that some population of leukocytes may be adsorbed in the column and removed from the blood circulation after treatment. To examine this hypothesis, we investigated the cellular components in the PMX columns after direct hemofiltration in four septic patients. We also investigated the humoral factors adsorbed on the PMX. For this purpose, the proteins attached to the filter were extracted and solubilized in PBS. Some of the proteins were purified chromatograpfically and their amino acid sequences were analyzed. Less

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (35 results)

All 2005 2004 2003 Other

All Journal Article (29 results) Publications (6 results)

  • [Journal Article] Differential effect of LFA703, pravastatin, and fluvastatin on production of IL-18 and expression of ICAM-1 and CD40 in human monocytes.2005

    • Author(s)
      Takahashi HK
    • Journal Title

      Journal of Leukocyte Biology 77(3)

      Pages: 400-407

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] alpha1-Adrenergic Receptor Antagonists Induce Production of IL-18 and Expression of ICAM-1 and CD40 in Human Monocytes.2005

    • Author(s)
      Takahashi HK
    • Journal Title

      Journal of Immunotherapy 28(1)

      Pages: 40-43

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inducible histamine protects mice from P.acnes-primed and LPS-induced hepatitis through H2-receptor stimulation.2004

    • Author(s)
      Yokoyama M
    • Journal Title

      Gastroenterology 127(3)

      Pages: 892-902

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Histamine inhibits lipopolysaccharide-induced interleukin (IL)-18 production in human monocytes.2004

    • Author(s)
      Takahashi HK
    • Journal Title

      Clin Immunol 112

      Pages: 30-34

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Histamine inhibits lipopolysaccharide-induced interleukin (IL)-18 production in human monocytes.2004

    • Author(s)
      Takahashi HK
    • Journal Title

      Clinical Immunology 112(1)

      Pages: 30-34

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Beta 2-adrenergic receptor agonist induces IL-18 production without IL-12 production.2004

    • Author(s)
      Takahashi HK
    • Journal Title

      Journal of Neuroimmunology 151(1-2)

      Pages: 137-147

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Analysis of sensitization to carboxymethylcellulose : identification of high risk group using ELISA and histamine release experiment.2004

    • Author(s)
      Mori S
    • Journal Title

      Inflammation Research 53

      Pages: 164-169

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] E-prostanoid (EP)2/EP4 receptor-dependent maturation of human monocyte-derived dendritic cells and induction of helper T2 polarization.2004

    • Author(s)
      Kubo S
    • Journal Title

      J.Pharmacology and Experimental Therapeutics 309(3)

      Pages: 1213-1220

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of beta2-adrenergic receptor agonists on intercellular adhesion molecule (ICAM)-1,B7,and CD40 expression in mixed lymphocyte reaction.2004

    • Author(s)
      Tamura R
    • Journal Title

      Transplantation 77(2)

      Pages: 293-301

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inducible histamine protects mice from Propionibacterium acnes and LPS-induced hepatitis through H2-receptor stimulation.2004

    • Author(s)
      Yokoyama et al.
    • Journal Title

      Gastroenterology 127(3)

      Pages: 892-902

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Histamine inhibits lipopolysaccharide-induced interleukin (IL)-18 production in human monocytes.2004

    • Author(s)
      Takahashi et al.
    • Journal Title

      Clin Immunol. 112(1)

      Pages: 30-34

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Differential effect of prostaglandins E_1 and E_2 on lipopolysaccharide-induced adhesion molecule expression on human monocytes.2003

    • Author(s)
      Takahashi HK
    • Journal Title

      European Journal of Pharmacology 512(2-3)

      Pages: 223-230

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Unique regulation profile of prostaglandin e1 on adhesion molecule expression and cytokine production in human peripheral blood mononuclear cells.2003

    • Author(s)
      Takahashi HK
    • Journal Title

      J.Pharmacology and Experimental Therapeutics 307(3)

      Pages: 1188-1195

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] MAP kinase-mediated proliferation of DLD-1 carcinoma by the stimulation of protease-activated receptor 2.2003

    • Author(s)
      Jikuhara A
    • Journal Title

      Life Sciences 73

      Pages: 2817-2829

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Histamine downregulates CD14 expression via H2 receptors on human monocytes.2003

    • Author(s)
      Takahashi HK
    • Journal Title

      Clinical Immunology 108(3)

      Pages: 274-281

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The regulation of ICAM-1 and LFA-1 interaction by autacoids and statins : a novel strategy for controlling inflammation and immune responses.2003

    • Author(s)
      Nishibori M
    • Journal Title

      Journal of Pharmacological Sciences 92(1)

      Pages: 7-12

    • NAID

      130000073674

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nafamostat mesilate is an extremely potent inhibitor of human tryptase.2003

    • Author(s)
      Mori S
    • Journal Title

      Journal of Pharmacological Sciences 92

      Pages: 420-423

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of prostaglandin E2 on intercellular adhesion molecule-1 and B7 expression in mixed lymphocyte reaction.2003

    • Author(s)
      Morichika T
    • Journal Title

      Transplantation 75(12)

      Pages: 2100-2105

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Histidine-rich glycoprotein plus zinc reverses growth inhibition of vascular smooth muscle cells by heparin.2003

    • Author(s)
      Mori S
    • Journal Title

      Cell Tissue Res 312

      Pages: 353-359

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Involvement of proteinase-activated receptor-2 in mast cell tryptase-induced barrier dysfunction of bovine aortic endothelial cells.2003

    • Author(s)
      Sendo T
    • Journal Title

      Cell Signal 15

      Pages: 773-781

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The regulation of ICAM-1 and LFA-1 interaction by autacoids and statins : a novel strategy for controlling inflammation and immune responses.2003

    • Author(s)
      Nishibori M
    • Journal Title

      Journal of Pharmacological Sciences 92

      Pages: 7-12

    • NAID

      130000073674

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] High affinity binding of histidine rich glycoprotein to nickel-nitrilotriacetic acid : the application to microquantification.2003

    • Author(s)
      Mori S
    • Journal Title

      Life Sci 73

      Pages: 93-102

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of β2-agrenergic receptor stimulation on IL-18-induced intercellular adhesion molecule-1 expression and cytokine production.2003

    • Author(s)
      Takahashi KH
    • Journal Title

      J Pharmacol Exp Ther 304

      Pages: 634-642

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Histamine inhibits lipopolysaccharide-Induced Tumor Necrosis Factor-α Production in an Intercellular Adhesion Molecule-1 and B7.1-Dependent Manner.2003

    • Author(s)
      Morichika T
    • Journal Title

      J Pharmacol Exp Ther 304

      Pages: 624-633

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prostaglandin E1-initiated immune regulation during human mixed lymphocyte reaction.

    • Author(s)
      Takahashi HK
    • Journal Title

      Clinical Immunology. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differential effect of LFA703 from pravastatin and fluvastatin on production of IL-18 and expression of ICAM-1 and CD40 in human monocytes.

    • Author(s)
      Takahashi et al.
    • Journal Title

      J Leuk Biol. (In press.)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Prostaglandin E1-initiated immune regulation in human mixed lymphocyte reaction.

    • Author(s)
      Takahashi et al.
    • Journal Title

      Clin Immunol. (In press.)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Differential effect of PGE1 and PGE2 on LPS-induced adhesion molecules expression on monocytes.

    • Author(s)
      Takahashi et al.
    • Journal Title

      Eur J.Pharmacol. (In press.)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] α1-Adrenergic receptor antagonists induce production of IL-18 and expressi of ICAM-1 and CD40 in human monocytes.

    • Author(s)
      Takahashi et al.
    • Journal Title

      J.Immunother. (In press.)

    • Related Report
      2004 Annual Research Report
  • [Publications] Mori et al.: "Histidine-rich glycoprotein plus zinc reverses growth inhibition of vascular smooth muscle cells by heparin"Cell Tissues Res. 312. 353-359 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mori et al.: "High affinity binding of serum histidine-rich glycoprotein to nickel-nitriloacetic acid : the application to microquantification"Life Sciences. 73. 93-102 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishibori, Takahashi, Mori.: "The regulation of ICAM-1 and LFA-1 interaction by autacoids and statins a novel strategy for controlling inflammation and immune・・・"J Pharmacol Sciences. 92. 7-12 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takahashi et al.: "Effects of beta2-adrenergic receptor stimulation on IL-18-induced ICAM-1 expression and cytokine production"J Pharmacol Exp Ther. 304. 634-642 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Morichika et al.: "Histamine inhibits lipopolysaccharide-induced TNF-a production in an ICAM-1- and B7.1-dependent manner"J Pharmacol Exp Ther. 304. 624-633 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takahashi et al.: "Unique regulation profile of prostaglandin E1 on adhesion molecule expression and cytokine production in human peripheral blood mononuclear・・・"J Pharmacol Exp Ther. 307. 1188-1195 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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