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1996 Fiscal Year Final Research Report Summary

MOLECULAR CELL BIOLOGICAL STUDIES ON EXPRESSION MECHANISM OF TISSUE FACTOR IN ENDOTHELIAL CELLS.

Research Project

Project/Area Number 07672355
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NAKAMURA Shin  PRIMATE RESEARCH INSTITUTE,KYOTO UNIVERSTIY INSTRUCTOR, 霊長類研究所, 助手 (10101255)

Co-Investigator(Kenkyū-buntansha) ITO Youko  AICHI MEDICAL SCHOOL,FACULTY OF MEDICINE,LECTURER., 医学部, 講師 (60065597)
GOTO Shunji  PRIMATE RESEARCH INSTITUTE,KYOTO UNIVERSITY INSTRUCTOR., 霊長類研究所, 助手 (90093343)
Project Period (FY) 1995 – 1996
KeywordsEndothelial Cells / Monocytes / Neutrophils / Tissue Factor / Thrombosis / Atherosclersis / 動脈硬化
Research Abstract

Tissue factor (thromboplastin, factor III) is a receptor-like membrane protein expressed on cell surface to initiate blood coaqulation cascade reaction through binding with plasma factor VII/VIIa. Tissue factor is known tobe expressed in endothelial cells, neutrophils and/or monocytes only upon their stimulation with LPS,cytokines, stress, PAF,and other inflammatory mediators. Hyperexpression of tissue factor of these cells directly causes abnormal hypercoagulopathy including thrombosis in brain and/or heart.
In this project We investigate expression mechanism and fucntion of tissue factor in endothelial cells, neutrophils and/or monocytes on molecular cell biological bases. We also studied on in vivo mechanism of tissue factor-mediated intravascular coagulation or thrombosis. Followings are research results in this project.
1.Research techniques of sandwich ELISA,flow-cytometry, immunohistochmical stain, RT-PCR were established to investigate expression mechanism of tissue factor on molecular cell biological bases.
2.The expression and clearance mechanisms (vesicle shedding and endocytosis) of tissue factor in LPS-stimulated human endothelial cells were studied.
3.A regulation mechanism by shear stress to cytokine-mediated tissue factor expression by human endothelial cells was deduced on gene transcriptional level.
4.A new neutrophil function to express tissue factor was found. This neutrophil tissue factor expression was mediated by an interaction between endothelial cells and leukocytes and suggested to be a possible causes of intravascular coagulation or thrombosis by in vivo studies.
5.Another new finding was signal transducing function of tissue factor in monocytes. This function was triggered by binding with factor VII/VIIa on cell surface and mediated by tissue factor associated gamma-chain.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] K. Kario, et al: "Merked Inerease of Actroted Factor VII in Upemic Patients" Throm bosis and Haemostasis. 73. 763-767 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Asakura, et al: "Role of Rssue Factor in Disseminated Intravasculer Cosegrlation" Thrombosis Research. 80. 217-224 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A. Higuri, et al: "Maccophagls and Neutrophils Inbiltrating into the liver on Responsible for Tissue Factor Expression" Thrombosis and Haemostasis. 75. 791-795 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Masuda, et al: "Association of Tissue Factor with a γ chein Homodimer of the Ig E Recip for Type I in Cultuid Human Monocytes" Europesr Journal of Immunology. 26. 2529-2532 (1996)

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      「研究成果報告書概要(和文)」より
  • [Publications] H. Kagawa, et al: "Tissue Factor on Small Vesicles of LPS-Stimulated Human vasculer Endothelial Cells" Theom bosis and Haemostasis. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y. Matsumoto: "Fluid Shser Stress Attenuoty Thrombomodulin Factor Molucal Nectorsis Focter niduaiol Fissue Facter Exprcxnion in Cultuad Enoletoliol Cells" Blood. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Kario, T.Matsuo, M.Matsuo, M.Koide, T.Yamada, S.Nakamura, T.Sakata, H.Kato, T.Miyata: "Marked Increase of Activated Factor VII in Uremic Patients." Thrombosis and Haemostasis. 73. 763-767 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Asakura, Y.Kamikubo, A.Goto, Y.Shiratori, M.Yamazaki, H.Jokaji, M.Saito, C.Uotani, I.Kumabashira, K.Aoshima, S.Nakamura, T.Matsuda: "Role of Tissue Factor in Disseminated Intravascular Coagulation." Thrombosis Research. 80. 217-224 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A.Higure, K.Okamoto, K.Hirata, H.Todoroki, Y.Nagafuchi, S.Takeda, H Katoh, H.Itoh, K.Ohsato, S.Nakamura: "Macrophages and Neutrophils Infiltrating into the Liver are Responsible for Tissue Factor Expression in a Rabbit Model of Acute Obstructive Cholangitis." Thrombosis and Haemostasis. 75. 791-795 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Masuda, S.Nakamura, T.Murakami, Y.Komiyama, H.Takahashi: "Association of Tissue Factor with a gamma chain homodimer of the IgE Receptor Type I in Cultured Human Monocytes." European Journal of Immunology. 26. 2529-2532 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Kagawa, Y.Komiyama, S.Nakamura, T.Miyake, Y.Miyazaki, K.Hamamoto, M.Matsuda, H.Takahashi, S.Nomura, S.Fukuhara: "Expression of Functional Tissue Factor on Small Vesicles of Lipopolysaccharide-Stimulated Human Vasucular Endothelial Cells." Thrombosis and Haemostasis. (in press).

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      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Matsumoto, Y.Kawai, K.Watanabe, M.Murata, M.Handa, S.Nakamura, and Y.Ikeda: "Fluid Shear Stress Attenuates Tumor Necrosis Factor Induced Tissue Factor Expressed in Cultured Endotherial Cells." Blood. (in press).

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

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Published: 1999-03-09  

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