Journal
BLOOD
Volume 105, Issue 1, Pages 145-152Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2004-02-0464
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Funding
- NHLBI NIH HHS [P01 HL044612, HL-56027, HL-44612, HL-33721, R01 HL033721, R24 HL063098, HL-63 098] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL056027, P01HL044612, R24HL063098, R29HL056027, R01HL033721] Funding Source: NIH RePORTER
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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-Palacle 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. (Blood. 2005;105:145-152) (C) 2005 by The American Society of Hematology.
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