Definition/Introduction

Weibel-Palade bodies are small storage granules located in endothelial cells comprising the intima of the heart and blood vessels. They are found in arteries, capillaries, veins, and the endocardium, but notably not in the lymphatic vessels. These bodies function to store 2 principal molecules, P-selectin and Von Willebrand factor. These 2 agents play a role in inflammation and hemostasis.

Von Willebrand factor (vWF) is essential for blood coagulation[1]. It functions to bind coagulation factor VIII in the presence of vessel injury. vWF then cross-links the basement membrane collagen of the vessel to gp1b seen on platelets. This process of platelet adhesion is one of the first steps of clot formation and maturation. P-selectin plays a major role in the ability to increase the permeability of endothelial cells, permitting the components of the cell-mediated immune system (leukocytes) to roll, marginate, and enter the extracellular focus of inflammation. P-selectin also plays a role in platelet aggregation, as it is activated and transported into the cell membrane by thrombin[1].

There are many other protein molecules stored in Weibel-Palade bodies, which include interleukin 8, endothelin 1, eotaxin-3, osteoprotegerin, angiopoietin-2, and alpha-1,3-fucosyltransferase VI. These are mediators of inflammation, immune response, angiogenesis, and vessel caliber and response to stressors.

Weibel-Palade bodies manufacture all these protein molecules and assemble them in the Golgi complex. Immature Weibel-Palade bodies are often located near the cell nucleus, where they acquire most membrane proteins. As they mature the Weibel-Palade bodies, disperse along microtubules. With time, Weibel-Palade bodies may also diffuse with their bodies to form large congregations.

Issues of Concern

The factor VIII that is packaged in Weibel-Palade bodies is produced largely in the endothelial cells, rather than in the liver alongside the other coagulation factors, as previously thought.[2] Due to their role in hemostasis, inflammation, and angiogenesis, it has been proposed that targeted inhibitors of exocytosis could treat inflammatory or thrombotic conditions[3].

Clinical Significance

The main source of vWF is the Weibel-Palade bodies. When there is an injury or bleeding, the Weibel-Palade bodies fuse and then secrete vWF. Degranulation can also be stimulated through the release of DDAVP (desmopressin), which can be useful in treating patients who underexpress or are missing vWF. vWF deficiency occurs in about 1% of the population, making it the most common inherited bleeding disorder[4]. The disorder may present as recurrent mucocutaneous bleeding or prolonged bleeding after minor trauma. The deficiency in vWF occurs due to aberrant production of the protein (decreased or misfolded) in the presence of a deleterious polymorphism. Weibel-Palade bodies are rarely absent, except in the context of this factor deficiency, and can be viewed with the use of electron microscopy.