Arteriosclerosis and Thrombosis, Vol 14, 990-999, Copyright © 1994 by American Heart Association

ARTICLES

Morphological alterations in endothelial cells associated with the release of von Willebrand factor after thrombin generation in vivo

M Richardson, S Tinlin, M De Reske, S Webster, Y Senis and AR Giles
Department of Pathology, Richardson Laboratory, Queen's University, Kingston, ON, Canada.

von Willebrand factor (vWF) is synthesized by endothelial cells and stored in endothelium-specific granules, the Weibel-Palade (WP) bodies. The release of vWF from endothelial cells in vitro in response to secretagogues such as thrombin is considered to result in the loss of WP bodies through the fusion of the WP bodies with the plasma membrane. Biochemical and morphological techniques, including transmission (TEM) and scanning (SEM) electron microscopy, were used to examine the plasma profile of vWF in parallel with morphological alterations in endothelial cells associated with the generation of thrombin in vivo. There was a rapid loss of high-molecular-weight multimers of the circulating vWF, with full recovery within 1 hour. Simultaneously, TEM demonstrated that the endothelial cells lost WP bodies and became severely vacuolated; this was associated with the appearance of craters in the endothelial surface on SEM. Release of stored vWF in WP bodies seemed to follow the fusion of multiple rather than individual WP bodies, with the resulting vacuole fusing and rupturing through the plasmatic membrane. Within 1 hour there was increased morphological evidence of metabolic organelle activity associated with replacement of WP bodies, presumably due to de novo synthesis of the basic protomer and its packaging in high-molecular-weight multimeric form in the storage organelles.

This article has been cited by other articles:

				C. Zhou, H. Chen, F. Lu, H. Sellak, J. A. Daigle, M. F. Alexeyev, Y. Xi, J. Ju, J. A. van Mourik, and S. Wu Cav3.1 ({alpha}1G) controls von Willebrand factor secretion in rat pulmonary microvascular endothelial cells Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L833 - L844. [Abstract] [Full Text] [PDF]

				S. Wu, J. Haynes Jr, J. T. Taylor, B. O. Obiako, J. R. Stubbs, M. Li, and T. Stevens Cav3.1 ({alpha}1G) T-Type Ca2+ Channels Mediate Vaso-Occlusion of Sickled Erythrocytes in Lung Microcirculation Circ. Res., August 22, 2003; 93(4): 346 - 353. [Abstract] [Full Text] [PDF]

				T. Romani de Wit, M. G. Rondaij, P. L. Hordijk, J. Voorberg, and J. A. van Mourik Real-Time Imaging of the Dynamics and Secretory Behavior of Weibel-Palade Bodies Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 755 - 761. [Abstract] [Full Text] [PDF]

				G Zupancic, D Ogden, C J Magnus, C Wheeler-Jones, and T D Carter Differential exocytosis from human endothelial cells evoked by high intracellular Ca2+ concentration J. Physiol., November 1, 2002; 544(3): 741 - 755. [Abstract] [Full Text] [PDF]

				J. B. Rosenberg, J. S. Greengard, and R. R. Montgomery Genetic Induction of a Releasable Pool of Factor VIII in Human Endothelial Cells Arterioscler Thromb Vasc Biol, December 1, 2000; 20(12): 2689 - 2695. [Abstract] [Full Text] [PDF]

				J.J. Emeis, Y. v. d. Eijnden-Schrauwen, C.M. v. d. Hoogen, W. d. Priester, A. Westmuckett, and F. Lupu An Endothelial Storage Granule for Tissue-Type Plasminogen Activator J. Cell Biol., October 6, 1997; 139(1): 245 - 256. [Abstract] [Full Text] [PDF]

				C. Lupu, F. Lupu, U. Dennehy, V. V. Kakkar, and M. F. Scully Thrombin Induces the Redistribution and Acute Release of Tissue Factor Pathway Inhibitor From Specific Granules Within Human Endothelial Cells in Culture Arterioscler Thromb Vasc Biol, November 1, 1995; 15(11): 2055 - 2062. [Abstract] [Full Text]