Biogenesis and exocytosis of Weibel-Palade bodies

Vascular endothelial cells contain typical, elongated vesicles, the so-called Weibel-Palade bodies, which serve as a storage compartment for von Willebrand factor (VWF), a plasma protein that plays an essential role in controlling the adhesion and aggregation of platelets at sites of vascular injury. Upon activation of endothelial cells by agonists such as thrombin, epinephrine or histamine, the Weibel-Palade bodies fuse with the plasma membrane and release their contents into the blood circulation. This process provides an adequate means by which endothelial cells can actively participate in controlling the arrest of bleeding upon vascular damage. Besides VWF, Weibel-Palade bodies contain a subset of other proteins, including interleukin-8 (IL-8), P-selectin and endothelin. Similar to VWF, these proteins are transported to the outside of the cell upon stimulation and may control local or systemic biological effects, including inflammatory and vasoactive responses. Apparently, endothelial cells are able to create a storage pool for a variety of bioactive molecules which can be mobilised upon demand. Endothelial cells that are deficient of VWF synthesis are not only unable to form Weibel-Palade bodies, but also lack the ability to store IL-8 or P-selectin or release these proteins in a regulated manner. It thus appears that VWF not only plays a prominent role in controlling primary haemostasis, but also may modulate inflammatory processes through its ability to target inflammatory mediators to the regulated secretion pathway of the endothelium