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2002 Fiscal Year Final Research Report Summary

Analysis of CS5 co-receptor molecule that specifically inhibits chemotaxis of polymorphonuclear leukocytes

Research Project

Project/Area Number 12470058
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionKumamoto University

Principal Investigator

YAMAMOTO Tetsuro  Kumamoto University, Graduate School of Medical Science, Professor, 大学院・医学研究科, 教授 (60112405)

Co-Investigator(Kenkyū-buntansha) NISHINO Norikazu  Kyushu Institute of Technology, Faculty of Engineering, Professor, 工学部, 教授 (40145165)
NAKAYAMA Hitoshi  Kumamoto University, Faculty of Pharmaceutical Science, Professor, 薬学部, 教授 (70088863)
SEMBA Umeko  Kumamoto University, School of Medicine, Faculty Member, 医学部附属病院, 助手 (50109691)
Project Period (FY) 2000 – 2002
Keywordsribosomal protein / leukocyte / chemotaxis / C5a receptor / apoptosis / transglutaminase / inflammation / antagonist
Research Abstract

The cross-linked dimer of RP S19 attracted monocytes as an agonist of C5a receptor. On the other hand, the same molecule inhibited the chemotaxis of polymorphonuclear leukocytes (PMN) as an antagonist of the C5a receptor. We initially identified the ligand moieties of the RP S19 dimer to the C5a receptor of monocytes. The RP S19 dimer bound to the C5a receptor by a two-step mechanism. The first ligand and second ligand moieties were identified to be-Lys41-His42-Lys43- and -Leu131-Asp132-Arg133-, respectively.
Next, we identified a switch moiety on the RPS19 dimer molecule, which converted the agonist function to the antagonist in the C5a receptor-mediated chemotaxis of PMN. The switch moiety was identified to be from Ile134 to Lys144 (IAGQVAAANKK), which was present following to the second ligand moiety.
We made a hypothesis that PMN had a molecule near the C5a receptor, which negatively regulated the intracellular signaling raised by the activated C5a receptor. Then we have been trying to identify the co-receptor molecule. We have prepared a subtraction cDNA library between a PMN cDNA pool and a monocyte cDNA pool. We have tried to prepare an analogue peptide with the second ligand moiety and the switch moiety that bore a fluorescence-labeled photosensitive chemical modifier. However, we have not succeeded to identify the co-receptor molecule of the PMN C5a receptor.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] T.Yammaoto: "Identification of C5a receptor antagonist moiety in monocyte chemotactic S19 protein dimer"Microcirculation annual. 18. 55-56 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Tokita, T.Yammaoto: "Polymorphonuclear leukocyte-dependent and -independent mechanisms in complement C5a-induced vascular permeability enhancement"Microcirculation annual. 18. 57-58 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shrestha Arjun 他7名: "Switch Moiety in Agonist/Antagonist Dual Effect of S19 Ribosomal Protein Dimer on Leukocyte Chemotactic C5a Receptor"American Journal of Pathology. 162(4). 1381-1388 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Yamamoto: "Molecular mechanism of monocyte predominant infiltration chronic inflammation : Mediation by a novel monocyte chemotactic factor,S19 ribosomal protein dimer"Pathol. Internat.. 50. 863-871 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Nishimura et al.: "Apoptotic cells of an epithelial cell lines, AsPC-1, release moncyte chemotactic S19 ribosomal protein dimer"J. Biochem.. 129. 445-454 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Shibuya et al.: "Identification of receptor-binding sites of monocyte chemotactic S19 ribosomal protean dimar"Am. J. Pahtol.. 159(6). 2293-2301 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Tokita et al.: "Functional difference between polymorphonuclear leukocytes and monocytes in terms of vascular permeability enhancement"Microcirculation annual. 17. 81-82 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Yammaoto: "Identification of C5a receptor antagonist moiety in monocyte chemotactic S19 protein dimer"Microcirculation annual. 18. 55-56 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Tokita and T. Yammaoto: "Polymorphonuclear leukocyte-dependent and -independent mechanisms in complement C5a-induced vascular permeability enhancement"Microcirculation annual. 18. 57-58 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Shrestha et al.: "Switch Moiety in Agonist/Antagonist Dual Effect of S19 Ribosomal Protein Dimer on Leukocyte Chemotactic C5a"Am. J. Pathol.. 162. 1381-1388 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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