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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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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
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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

From the Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; Institut Fédératif de Recherche No 4, Hôpital Cardiologique, Pessac, France; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI; and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA.

We have previously reported that ectopically expressed factor VIII (FVIII) is stored within platelets and is released upon platelet activation. Studies by others in various cell lines have suggested that having von Willebrand factor (VWF) coexpression is 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 needs to be elucidated. (Blood. 2005;105:4674-4676)


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