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Role of Macrophages and Immune Cells in Atherogenesis

Research Project

Project/Area Number 04454181
Research Category

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

Allocation TypeSingle-year Grants
Research Field Human pathology
Research InstitutionUniversity of Tsukuba

Principal Investigator

WATANABE Teruo  Inst.Basic M.Sci., University of Tsukuba Professor, 基礎医学系, 教授 (40037396)

Co-Investigator(Kenkyū-buntansha) SHIMOKAMA Tatsuro  Inst.Basic M.Sci., University of Tasukuba Assist.Prof., 基礎医学系, 講師 (50170999)
菅間 博  筑波大学, 基礎医学系, 講師 (10195191)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1993: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1992: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsAtherogenesis / Atherosclerosis / Macrophages / T lymphocytes / Immune Mechanism / Foam Cells / In Vitro Model / Hypercholesterolemia
Research Abstract

(1) To elucidate the role of T lymphcytes and macrophages in human atherosclerosis, the localization of various cytokines with an analysis of immunophenotypic featues of the cellular initlrates was studied in normal aortas from children and in later phases of the disease, and the results suggested that a specific in situ, cell mediated hypersensitivity plays a pivotal role in the nascent as well as the progression stages of human atherogenesis.
(2) Temporal and spatial distribution of the immunologic components of atherosclerosis was studied in a diet-induced rat model. Analysis of cellular components by en face double immunostaining revealded that infiltration of T lymphocytes was most prominent in the incipient phase of lesion formation.
(3) In vivo functions of T lymphocytes relevant to atherogenesis was studied in diet-induced aortic lesions of athymic nude rats lacking T lymphocytes, and the results obtained demonstrated that, in comparison with control animals, the lesion development was limited in size, whereas foam cell transformation of intimal macrophages was more prominent in nude rats.
(4) We developed an in vitro model of the arterial intima for three dimensional analysis of vascular cell interactions relevant to atherogenesis, and ; induced fatty streak-like lesions by the use of blood mononulcear cells snd endothelial cell-modified low density lipoprotein.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Yamada,T.et al.: "Induction of fatty streak-like lesions in vitro using a culture model system simulating arterial intima" Am.J.Pathol.141. 1435-1444 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Baba,N.et al.: "Effects of hypercholesterolemia on initial and chronic phase of rat nephrotoxic serum nephritis:development of focal segmental glomerulosclerosis.analogous to atherosclerosis" Virchows Arch.B Cell Pathol.64. 97-105 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fan,J.et al.: "Monocyte-endothelial cell inter action in vitro,with reference to the influence of interleukin-1 and tumor necrosis factor" Biol.Cell. 79. 17-26 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kishikawa,H.et al.: "Localization of T lymphocytes and macrophages expressing IL-1,IL-2 receptor,IL-6 and TNF in human aortic intima.Role of cell mediated immunity in human atherogenesis" Virchows Arch.A Pathol.Anat.Histol.423. 433-442 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fan,J.et al.: "Activation and cholesterol accumulation of macrophages induced by hypercholesterolemia." Pathobiology. 62. 1-7 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Haraoka,S.et al.: "Participation of T lymphocytes in early atherogenesis:analysis of dietinduced aortic lesions of nude rats using en face double immunostaining" Atherosclerosis. 109. 100-101 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimokama,T.et al.: "Participation of T lymphocytes and macrophages in atherogenesis" J.Atheroscler.Thromb.1. s14-s20 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Watanabe,T.et al.: "T lymphocytes in atherosclerotic lesions" Ann.N.Y.Acad.Sci.(1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yamada, T.et al.: "Induction of fatty streak-like lesions in vitro using a culture model system simulating arterial intima" Am.J.Pathol. 141. 1435-1444 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Baba, N.et al.: "Effects of hypercholesterolemia on initial and chronic phase of rat nephrotoxic serum nephritis : development of focal segmental glomerulosclerosis, analogous to atherosclerosis" Virchows Arch.B Cell Pathol. 64. 97-105 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fan, J.et al.: "Monocyte-endothelial cell interaction in vitro, with reference to the influence of interleukin-1 and tumor necrosis factor" Biol.Cell. 79. 17-26 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kishikawa, H.et al.: "Localization of T lymphocytes and macrophages expressing IL-1, IL-2 receptor. IL-6 and TNF in human aortic intima.Role of cell mediated immunity in human atherogenesis" Virchows Arch.A Pathol.Anat.Histol. 423. 433-442 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fan, J.et al.: "Activation and cholesterol accumulation of macrophages induced by hypercholesterolemia." Pathobiology. 62. 1-7 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Haraoka, S.et al.: "Participation of T lymphocytes in early atherogenesis : analysis of dietinduced aortic lesions of nude rats using enface double immunostaining" Atherosclerosis. 109. 100-101 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimokama, T.et al.: "Participation of T lymphocytes and macrophages in atherogenesis" J.Atheroscler.Thromb. 1. s14-s20 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Watanabe, T.et al.: "T lymphocytes in atherosclerotic lesions" Ann.N.Y.Acad.Sci.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Haraoka S.et al.: "Oarticipation of T lymphocyles in early atherogenesis: Analysis of diet-induced aortjc lesions of nude rats using en face double immunostaining." Atherosclerosis. 109. 100-101 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shimokama T.et al.: "Participation of T lymphocytes and macrophages in atherogenesis." J Atheroscler.Thromb.1. S14-S20 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Watanabe T.et al.: "T lymphocytes in atherosclerotic lesions." Ann.N.Y.Acad.Sci.748. 40-56 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 渡辺照男、他: "内膜細胞(平滑筋細胞、マクロファージ、リンパ球)と動脈硬化" 病理と臨床. 12. 52-59 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 渡辺照男、他: "動脈硬化とマクロファージ/Tリンパ球" 血管と内皮. 4. 456-465 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hayato Kishikawa: "Localization of T lymphocytes and macrophages expressing IL-1,IL-2 receptor,IL-6 and TNF in human…" Virchows Arch A Pathol Anat Histol. 423. 433-442 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Jianglin Fan: "Monocyte-endothelial cell interactions in vitro,with reference to the influence of IL-1 and TNF" Biology of Cell. 79. 17-26 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Naoki Baba: "Effects of hypercholesterolemia on initial and chronic phases of rat nephrotoxic nephritis,development of…" Virchows Arch.B Cell Pathol. 64. 97-105 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takahiro Yamada: "Induction of fatty streak-like lesions in vitro using a culture model system simulating arterial intima" American Journal of Pathology. 141. 1435-1444 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Osamu Tokunaga: "Endothelin.Immunohistologic localization in aorta and biosynthesis by cultured human aortic endothelial cells." Laboratory Investigation. 67. 210-217 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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