Re-establishment of VWF-dependent Weibel-Palade bodies in VWD endothelial cells. Blood 2005 Jan 01;105(1):145-52
Date
08/28/2004Pubmed ID
15331450Pubmed Central ID
PMC3938105DOI
10.1182/blood-2004-02-0464Scopus ID
2-s2.0-11144247649 (requires institutional sign-in at Scopus site) 55 CitationsAbstract
Type 3 von Willebrand disease (VWD) is a severe hemorrhagic defect in humans. We now identify the homozygous mutation in the Chapel Hill strain of canine type 3 VWD that results in premature termination of von Willebrand factor (VWF) protein synthesis. We cultured endothelium from VWD and normal dogs to study intracellular VWF trafficking and Weibel-Palade body formation. Weibel-Palade bodies could not be identified in the canine VWD aortic endothelial cells (VWD-AECs) by P-selectin, VWFpp, or VWF immunostaining and confocal microscopy. We demonstrate the reestablishment of Weibel-Palade bodies that recruit endogenous P-selectin by expressing wild-type VWF in VWD-AECs. Expression of mutant VWF proteins confirmed that VWF multimerization is not necessary for Weibel-Palade body creation. Although the VWF propeptide is required for the formation of Weibel-Palade bodies, it cannot independently induce the formation of the granule. These VWF-null endothelial cells provide a unique opportunity to examine the biogenesis of Weibel-Palade bodies in endothelium from a canine model of type 3 VWD.
Author List
Haberichter SL, Merricks EP, Fahs SA, Christopherson PA, Nichols TC, Montgomery RRAuthor
Robert R. Montgomery MD Adjunct Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Aorta
Base Sequence
Cells, Cultured
Dogs
Endothelial Cells
Frameshift Mutation
Gene Expression Regulation
Humans
Molecular Sequence Data
Protein Processing, Post-Translational
Weibel-Palade Bodies
von Willebrand Diseases
von Willebrand Factor
