Re-establishment of VWF-dependent Weibel-Palade bodies in VWD endothelial cells.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Haberichter SL,Merricks EP,Fahs SA,Christopherson PA,Nichols TC,Montgomery RR

doi

10.1182/blood-2004-02-0464

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

145-52

issue

1

eissn

0006-4971

issn

1528-0020

pii

2004-02-0464

journal_volume

105

pub_type

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