Physiological roles of lymphatic endothelial cells on lymph formation and transport

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ACTIVATED MACROPHAGE-MEDIATED ENDOGENOUS PROSTAGLANDIN AND NITRIC OXIDE-DEPENDENT RELAXATION OF LYMPHATIC SMOOTH MUSCLESThe 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 HEPARINWe 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