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Studies on Immunobiological Mechanisms in Atherogenesis

Research Project

Project/Area Number 07457047
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionUniversity of Tsukuba

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) SHIMOKAWA Tatsuro  Univ.of Tsukuba, Inst.of Basic Med.Sci.Ass Professor, 基礎医学系, 助教授 (50170999)
范 江霖  筑波大学, 基礎医学系, 講師 (60272192)
原岡 誠司  筑波大学, 基礎医学系, 助手 (40251053)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥4,300,000 (Direct Cost: ¥4,300,000)
KeywordsAtherosclerosis / Hypercholesterolemia / Macrophage / Foam cell T cell / Vascular dendritic cell / Adhesion Molecule / Endothelin-1 / 酸化LDL / 高脂血症 / 泡沫細胞 / ヌードラット / 内皮細胞 / 立体培養 / 泡沫化
Research Abstract

(1) To elucidate the role of T cell-macrophage interactions in atherogeness we studied the distribution pattern of T cells and macrophages in T cell-depleted athymic homozygous (rnu/rnu) rats fed a cholesterol-enriched diet. In comparison with run/・・・rats, the lesion development was limited in size. whereas foam cell transformation of intimal macrophages was more prominent in rnu/rnu rats. (2) We found that cells from the family of antigen presenting dendritic cells reside in the intima of large arteries. These vascular dendritic cells (VDC) are common in atherosclerotic lesions, and express CDla and S-100. Present ultrastructural examination disclosed in the cytoplasm of VDC Birbeck granule-like structures that are uniquely present in Langerhans cells. Further studies using Lag antibody. which specifically stains Bioreck granules and Biobeck granule-associated structures in Langerhans cells demonstrated that Lag-positive cells were found in the aortic wall. The findings obtained mayimply that mechanisms of antigen presentaion migh be similar to those involved in atherosclerosis. (3) We demonstrated that ICAM-1 expression is up-regulated in the lesionprone areas of aorta in diet-induced hypercholesterolemic rats. Increased expression of [CAM-1 was associated with enhanced macrophage intimal recruitment. Injection of anti-ICAM-1/LFA-1 mab reduced macrophage adherence and their migration into the intima. These results suggest that the ICAM-1/LFA-1 pathway is involved in macrophage-endothelial cell interactions during the early stage of cholesterol-induced atherogenesis. (4) Using a three dimensional culture model simulating in vivo arterial intima. we provided evidence that nLDLs and oxidized LDLs may act as a potential mediator for the increased release of ET-1 in hyperlipidemia and atherosclerosis.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Haraoka, S.・Shimokama, T.・Watanabe, T.: "Role of Tlymphocytes in the pathogenesis of atherosclerosis Animal studies using athymic nude rats." Ann.N.Y.Acad.Sci.811. 515-518 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Bobry.Shev.Y.V.・Watanabe, T.: "Ultrastructural evidence for association of vascular dendritic cells with Tlymphocytes and with Blymphocytes in human atherosclera." J.Subreicrosc.Cytol.Pathol.29. 209-221 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Bobryshev.Y.・Watanabe.T.: "Subset of vascular dendritic cells transforming foam cells in human atherosclerotic lesions." Canliovasc.Pathol. 6. 321-331 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsumoto, S.・Katoh.M.・Saito, S.・Watanabe, , T.: "Identification of soluble type of membrane tyape matrix metalloproteinase 3 formed by alternative spliced mRNA." Biochem.Biophys.Acta. 1354. 159-170 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Bobryshev.Y.V.・Ikezawa, T.・Watanabe, T.: "Formation of Birbeck granule-like structures in vascular dendritic cells in human atherosdero ticaorta." Atherosclerosis. 133. 193-202 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugiyama, F.・Haraoka, S.・Watanabe, T.: "Acceleration of atherosclerotic lesions in transgenic mice with hypertension by the activated reninargio tersin system." Lab.Invest. 76. 835-842 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Haraoka.S..Shimokama, T..Watanabe.T.: "Role of T lymphocytesin the pathogenesis of atherosderosis Animal studies using athymic nude rats" Ann.N.Y.Acad.Sci. 811. 515-518 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Bobryshev.Y.V..Watanabe.T.: "Ultrastructural evidence for association of vascular dendritic cells with T lymphocytes and with B lymphocytes in human atherosderosis" J.Submicrosc.Cytol.Pathol. 29. 209-221 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Bobryshev.Y.V..Watanabe.T.: "Subset of vascular dendritic cells transforming into foam cells in human atherosderotic lesions" Canliovase.Pathol. 6. 321-331 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Matsumoto.S..Katoh.M..Saito.S..Watanabe.T., Masuho Y.: "Identification of soluble type of membrane type matrix metalloproteinase 3 formed by alternative spliced mRNA" Biochem.Biophys.Acta. 1354. 159-170 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Bodryshev.Y.V..Ikezawa.T..Watanabe.T: "Formation of Birbeck granule-like structures in vascular dendritic cells in human atherosderotic aorta Lag antibody to epidermal Langerhans cells recognizes cells n the aortic wall" Atherosderosis. 133. 193-202 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugiyama.F..Haraoka.S..Watanabe.T..Shiota.N..Taniguchi.K.Ueno.Y..Tanimoto.K..Murakami.K..Fukamizu.A..Yagami.K.: "Acceleration of atherosderoticlesions in transgenic mice with hypertension by the activated reninangiotensin system." Lab.Invest. 76. 835-842 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nie.Q..Fan.J..Haraoka.S..Shimokama.T..Watanabe.T.: "Inhibition of mononudear cell recruitmentin aortic intima by treatment with anti-ICAM-1 and anti-LFA-1 monodonal antibodies in hypercholesterolemic rats Implications of the ICAM-1 and LFA-1 pathway in atherogenesis." Lab.Invest. 77. 469-482 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Haraoka S, Shimokawa T, Watanabe T: "Role of T lymphocytes in the pathogenesis of atherosclerosis,Animal studies using athymic nude rats" Annals of New York Academy of Sciences. 811. 515-518 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Bobryshev Y.V, Ikezawa T, Watanabe T.: "Formation of Birbeck granule-like structures in vascular dendritic cells in human atherosclerotic aorta" Atherosclerosis. 133. 193-202 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nie Q, Fan J, Haraoka S, et al: "Inhibition of mono nuclear cell recruitment in aortic intina by treatment with anti-ICAM-1 and anti-LFA-1 monoclonal" Laboratory Investigation. 77. 469-482 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Watanabe,T et al.: "Inflammatory and immune nature of atherosclerosis." Int.J.Cardiol.54. s25-s34 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsumoto,S et al.: "Molecular cloning of rabbit matrix metalloproteinase-2 and its broad expression at several tissues." Bioch.Biophys.Acta. 1307. 137-139 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Uyama,H et al.: "Diet-induced hypercholesterolemia increases endothelin-1 release by aortic endothelial cells." Pathobiology. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Bobryshev,Y.V et al.: "Ultrastructural evidence for association of vascular dendritic cells with T-lymphocytes and B-cells in・・・・・・" J.Subnicrosc.Cytol.Pathol.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Haraoka,S et al.: "Role of T lymphocytes in the pathogenesis of atherosclerosis:Animal studies using athymic nude rats." Ann.N.Y.Acad.Sci.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Watanabe,T.et al.: "T lymphocytes in atherosclerotic lesions." Ann.N.Y.Acad.Sci.748. 40-56 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Haraoka,S.et al.: "Participation of T lymphocytes in atherogenesis:sequential and quantitative observation of aortic・・・" Virchows Arch.426. 307-315 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shimokama.T.et al.: "Morphological fate and sequelae of human atherosclerosis:Evaluation of immune mechanisms in atherogenesis・・・" Pathol.Internat.45. 801-814 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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