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Physiological roles of lymphatic endothelial cells on lymph formation and transport

Research Project

Project/Area Number 08457009
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionShinshu University

Principal Investigator

OHHASHI Toshio  Dept.of Physiol., Shinshu Univ.Sch.of Med., Chairman and Professor, 医学部, 教授 (80020832)

Co-Investigator(Kenkyū-buntansha) IKOMI Fumitaka  Dept.of Physiol., Shinshu Univ.Sch.of Med., Associate Professor, 医学部, 助教授 (50262704)
WANG Haiije  Dept.of Physiol., Shinshu Univ.Sch.of Med., Research Associate
横山 伸  信州大学, 医学部, 助手
王 海じぇ  信州大学, 医学部, 助手
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥5,300,000 (Direct Cost: ¥5,300,000)
Keywordsinfiltrated macrophage / macrophages-derived vasoactive agents / nitric oxide / vasodilative prostanoids / bFGF / cultured lymphatic endothelial cells / heparin / lymphangiogenesis / リンパ管新生 / リンパ管内皮細胞 / ウーンドアッセイ法 / 細胞増殖と遊走 / 管腔形成 / タイプIコラーゲン / モノクロナールED1抗体 / リンパ管平滑筋 / 弛緩反応 / Bacterial LPS / nitric oxide(NO) / 血管拡張性プロスタグランジン(PG_S) / NOとPG_sの共分泌
Research Abstract

ACTIVATED MACROPHAGE-MEDIATED ENDOGENOUS PROSTAGLANDIN AND NITRIC OXIDE-DEPENDENT RELAXATION OF LYMPHATIC SMOOTH MUSCLES
The effects of macrophages activated by bacterial lipopolysaccharide (LPS) on the mechanical activity of lymph vessels with or without the endothelium were investigated using conventional bioassay preparations. The supematant of the macrophagtes suppressed significantly the basal tone of the lymphatic bioassay rings precontracted by U46619. The macrophage-induced vasodilation of the lymph vessels was significantly reduced by 12h preincubation of the macrophages with L-NAME,indomethacin, dexamethasone, or cycloheximide. Simultaneous preincubation of L-NAME and indomethacin caused a synergistic reduction of the macrophages-induced vasodilation of the lymphatic bioassay rings. These findings suggest that macrophages activated by bacterial LPS produce a marked relaxation of lymphatic smooth muscles through the co-release of nitric oxide and vasodilative prostaglandins.
BAS … More ICPFIBROBLAST GROWTH FACTOR-MEDIATED LYMPHANGIOGENESIS OF LYMPHATIC ENDOTHELIAL CELLS ISOLATED FROM DOG THORACIC DUCTS : EFFECTS OF HEPARIN
We have attempted to evaluate whether, similar to angiogenesis of blood vessels, cultures of lymphatic endothelial cells (LEC) isolated from dog thoracic ducts have an ability to induce lymphangiogenesis in response to basic fibroblast growth factor (bFGF) and then to examine effects of heparin on the bFGF-mediated morphogenesis. Effects of bFGF and/or heparin on proliferation and migration of the LEC were also evaluated by changing the number of the subconfluent cells and by wound migration assay, respectively. The effects of the agents on invasion and tube formation of the LEC into a three-dimensional collagen gel and on collagen gel-induced tube formation of the LEC were also investigated by a phase-contrast microscope and an electron microscope. The bFGF caused a significant induction of proliferation and migration of the LEC,the induction of which was augmented dose-dependently by an additional treatment with heparin ranging from 1 to 100 mug/ml. The bFGF produced invasion and tube formation of the LEC into a three-dimensional collagen gel. The bFGF also facilitated to form capillary-like tubes of the LEC between two layrs of colalgen gels. Heparin accelerated the both processes of the bFGF-mediated lymphangiogenesis of the LEC.These findings suggest that the cultured LEC isolated from dog thoracic ducts have an ability to form lymphatic capillary-like tubes in response to bFGF and that heparin accelerates does-dependently the process of the bFGF-mediated neovascularization of lymph vessels. Less

Report

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

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Fukaya, Y.Ohhashi, T.: "Acetylcholine-and flow-induced production and release of nitric oxide in arterial and venous endorhdial cells" American Journal of Physiology. 270. H99-H106 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ikomi, F.Schmid-Schaubein, G.W.: "Lymph pump mechanics in rabbit hindleg." American Journal of Physiology. 271. H173-H183 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Wang, H.J.Mizuno, R.Ohhashi, T.: "Macropbage-inoluced nitricoxide-and prostaglandins mediated relaxation in artiorial smooth muscles." Canadian Journal of Plysiology & Phowadcology. 75. 789-795 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshiro, Y.Ohhashi, T.: "Flow-and acetyleholine-mediated nitricoxide-and prostaglandins-dependent vosodilation in isolated rabbit spinal drteries." American Journal of Physiology. 270. H2217-H2223 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Zang, J.L, Yokoyama, S.Ohhashi, T.: "Inhibitory eflects of Huorescein isothiocyawate phatodetiration on lymphatu pcemp actolity" Microvaowlar Rosearch. 54. 99-107 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tom.Y.H.: "Basic fibro plast growth factor-mediated lymphangiogenesis of lymphotic endothelial cells isolated from dog tharacie ducts." Japanese Journal of Physiology. 42(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fukaya, Y., Ohhashi, T.: "Acetylcholine- and flow-induced production and release of nitric oxide in arterial and venous endothelial cells." Am.J.Physiol.270. H99-H106 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ikomi, F., Schmid-Schoeinbein, G.W.: "Lymph pump mechanics in rabbit hind leg." Am.J.Physiol.271. H173-H183 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Wang, H.J., Mizuno, R., Ohhashi, T.: "Macrophage-induced nitric oxide- and prostaglandins-mediated relaxation in arterial smooth muscles." Can.J.Physiol.Pharmacol.75. 789-795 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yashiro, Y., Ohhashi, T.: "Flow- and acetylcholine-mediated nitric oxide- and prostaglandins-dependent vasodilation in isolated rabbit spinal arteries." Am.J.Physiol.273. H2217-H2223

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Zang, J.L., Yokoyama, S., Ohhashi, T.: "Inhibitory effects of fluorescein isothiocyanate photoactivation on lymphatic pump activity." Microvasc.Res.54. 99-107 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tan, Y.H.: "Basic fibroblast growth fact-mediated lympyhangiogenesis of lymphatic endothelial cells isolated from dog thoracic ducts" Jpn.J.Physiol.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] KAMEI T, OHHASHI T et al: "Instrumentation for concarrent,dynamic monituring of active sweat glords and perspiration volume" INSTRUMENTATION,SCIENCE & TECHNOLOGY. 25. 39-53 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] WANG HJ, MIZUNO R, OHHASHI T.: "Macrophge-induced nitric oxide-and prostagandins-mediated reloxation in arterial smooth musiles" CANADIAN JOURNAL OF PHYSIOLOGY & PHAPMACOLOGY. 75. 789-795 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] WANG JX, IKOMI F, OHHASHI T.: "5-Hydroxytyptamine induced nitric oxide and pronoids -mediated relaxations in isolated dogautericr spiral small arteries" CANADIAN JOURNAL OF PHYSIOLOGY & PHAPAMCOLOGY. 75. 357-362 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] NISHIZAWA S, OHHASHI T. et al: "Capsaiein-induced nitric oxide-dependent relaxation in the isoloted dog urethra" EUROPEAN JOURNAL OF PHAAMACOLOBC. 335. 211-219 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] YASHIRO Y, OHHASHI T: "Flou-and acetylcholine-mediated nitric oxide-and prostaglavidins- dependent podilation in isolated rabbit spiral cliteredes" AMERICAN JOURNAL OF PHCSIOLOGY. 270. H99-H106 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] ZANG JL, YOKOYAMA S, OHHASHI T: "Inhibitory effects of fluoresention isothiocyanate photoactivation on lymphatic pump activity" MACROVASOULAR RESEARCH. 54. 99-107 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fukaya,Y.Ohhashi,T.: "Acetylcholine-and How-induced production and release of nitrlc oxide in arterial and renons endothelial cells" Am,J.Physiol.270. H99-H106 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ikomi,F.et al.: "Lymph pump mechanics in rabbit hird leg." Am.J.Physiol.271. H173-H183 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yokoyama,S.et al.: "Effects of bradykinin on lymphatic pumping in rat mesentery" Am.J.Physiol.270. G752-G756 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yokoyama,S.et al.: "Hypoxia-reoxygenation impairs endothdium-dependent relaxation in isdated rat aorta" Am.J.Physiol. 270. R1126-R1131 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ohigashi,Y.et al.: "Effects of 5-hydroxy tryptamine and actenosine on the canine isolated cerebral resistance vessels" Angiology. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Wang,H.J.: "Activated macrophages-mediated endogenous prostaglandins and nitric oxide-dependent relaxation of Lymphatic smooth muscles" Jpn,J.Physiol.(印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ohhashi,T.et al.: "Proceedings of 6th World Congress for Microcr culation (Monduzzi Editor,Italy)" Messmer,K.& Kubler,W.M., 1010 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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