The roles of Weibel-Palade bodies in processing and release of endothelin-1

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1) Dynamic changes in cultured human umbilical vein endothelial cells (HUVEC) after exposure to hypoxic condition were investigated by electron microscopy, and surpernants of the cultured media ware prepared for assays of ET-1 concentration by sandwich-EIA method. A remarkable increase in number of Weibel-Palade (WP) and elevation of ET-1 concentration in the media were confirmed in the hypoxic HUVEC, when compared to the normoxic one. The rat abdominal aorta under the hypoxic condition was investigated by electron microscopy, immunocytochemistry and in-situ hybridization. The significant increase in number of WP bodies uniquely occurred in the hypoxic samples. At the same time, the degree of immunoreactivity for ET-1 and that of ET-1 mRNA signal were significantly enhanced in the hypoxic samples when compared to the normoxic ones. These findings suggest that the correlation exists between increased WP bodies and enhanced synthesis and release of ET-1 in the hypoxic endothelial cells.2 … More ) The rat thoracic aorta after cadmium administration was prepared for electron microscopy and immunocytochemistry. A remarkable increase in number of WP bodies occurred in the endothelia of cadmium-treated rat. Immunoreactivity for ET-1 and ECE-1 was preferentially localized along the endothelium control groups, and the immunoreactive intensities of ET-1 and ECE-1 were significantly enhanced in the cadmium-treated groups. By immunoelectron microscopy, immunoreactive gold particles for ET-1 were preferentially localized in WP bodies and those for ECE-1 were in WP bodies as well as along the endothelial cell membrane in control groups. By cadmium administration, immunoreactivity for ET-1 and ECE-1 appeared to be enhanced, and immunoreactivity for ET-1 in WP bodies, which are closely associated with the endothelial cell membrane became more pronounced. Thus, the present findings suggest that the correlation exists between increased WP bodies and enhanced release of ET-1, which is processed by ECE-1 in WP bodies, in a manner of a regulated release by cadmium administration. Less