Richardson M, Tinlin S, De Reske M, Webster S, Senis Y, Giles A R
Department of Pathology, Richardson Laboratory, Queen's University, Kingston, ON, Canada.
Arterioscler Thromb. 1994 Jun;14(6):990-9. doi: 10.1161/01.atv.14.6.990.
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.
血管性血友病因子（vWF）由内皮细胞合成并储存于内皮细胞特异性颗粒即魏尔-帕拉德小体（WP小体）中。体外内皮细胞在诸如凝血酶等促分泌剂的作用下释放vWF，被认为是WP小体通过与质膜融合而丢失的结果。采用包括透射电子显微镜（TEM）和扫描电子显微镜（SEM）在内的生化和形态学技术，并行检测体内凝血酶生成相关的内皮细胞形态学改变时的vWF血浆谱。循环中的vWF高分子量多聚体迅速丢失，1小时内完全恢复。同时，TEM显示内皮细胞丢失WP小体并出现严重空泡化；这与SEM观察到的内皮表面坑洼的出现有关。WP小体中储存的vWF的释放似乎是多个而非单个WP小体融合的结果，形成的空泡通过质膜融合并破裂。1小时内，与WP小体替代相关的代谢细胞器活性的形态学证据增多，推测这是由于基本亚基的从头合成及其以高分子量多聚体形式包装于储存细胞器中所致。
