Project/Area Number |
08457009
|
Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General physiology
|
Research Institution | Shinshu 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)
|
Keywords | infiltrated 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
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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
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