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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4674-4676.
Prepublished online as a Blood First Edition Paper on February 24, 2005; DOI 10.1182/blood-2004-12-4701.


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Submitted December 13, 2004
Accepted February 21, 2005

Intracellular interaction of Von Willebrand Factor and Factor VIII depends on cellular context: lessons from Platelet Expressed Factor VIII

Helen Yarovoi, Alan T Nurden, Robert R Montgomery, Paquita Nurden, and Mortimer Poncz*

Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
IFR4, Hopital Cardiologique, Pessac, France
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

* Corresponding author; email: poncz{at}email.chop.edu.

We have previously reported that ectopically expressed Factor (F) VIII is stored within platelets and is released upon platelet activation. Studies in various cell lines by others have suggested that having Von Willebrand Factor (VWF) coexpression was necessary for FVIII granular storage and for its secretion. We tested the importance of VWF coexpression for ectopic storage of FVIII in platelets and for its bioavailability. Transgenic mice expressing platelet-specific FVIII were crossed onto a VWF-/- background. Antigenic levels of platelet FVIII in these mice were nearly unchanged whether VWF was present or not. Whole blood clotting times and FeCl3 carotid artery injury correction demonstrated that platelet FVIII demonstrably improved the bleeding diathesis in FVIIInull mice independent of the platelets' VWF status. Immunogold electron microscopy demonstrated that platelet FVIII is stored in platelet {alpha}-granules independent of the presence of VWF. It appears that FVIII's interaction with VWF and its intracellular transportation, storage and secretion differ greatly depending on the cell type. The molecular basis for these differences now need to be elucidated.


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