Weibel Palade Bodies

Article Author:
Daniel Kaufman
Article Editor:
Michael Costanza
Updated:
12/6/2018 6:38:34 PM
PubMed Link:
Weibel Palade Bodies

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 two principal molecules, P-selectin and Von Willebrand factor. These two agents play a role in inflammation and hemostasis. Von Willebrand factor is essential for blood coagulation[1]. It functions to bind coagulation factor VIII in the presence of vessel injury. vWF then cross-links 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/response to stressors.

Weibel-Palade bodies manufacture all these proteins 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 Von Willebrand factor is the Weibel-Palade bodies. When there is an injury or bleeding, the Weibel-Palade bodies fuse and then secrete Von Willebrand factor.  Degranulation can also be stimulated through release of DDAVP (vasopressin), which can be useful in treating patients who underexpress or are missing vWF. Von Willebrand factor 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 Von Willebrand factor 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.


References

[1] Kalagara T,Moutsis T,Yang Y,Pappelbaum KI,Farken A,Cladder-Micus L,Vidal-Y-Sy S,John A,Bauer AT,Moerschbacher BM,Schneider SW,Gorzelanny C, The endothelial glycocalyx anchors von Willebrand factor fibers to the vascular endothelium. Blood advances. 2018 Sep 25     [PubMed PMID: 30237293]
[2] Turner NA,Moake JL, Factor VIII Is Synthesized in Human Endothelial Cells, Packaged in Weibel-Palade Bodies and Secreted Bound to ULVWF Strings. PloS one. 2015     [PubMed PMID: 26473492]
[3] Nightingale TD,McCormack JJ,Grimes W,Robinson C,Lopes da Silva M,White IJ,Vaughan A,Cramer LP,Cutler DF, Tuning the endothelial response: differential release of exocytic cargos from Weibel-Palade bodies. Journal of thrombosis and haemostasis : JTH. 2018 Jun 28     [PubMed PMID: 29956444]
[4] Singh D,Natarajan A,Nand S,Mai HP, Genetics of Hypercoagulable and Hypocoagulable States. Neurosurgery clinics of North America. 2018 Oct     [PubMed PMID: 30223962]