Intracellular interaction of von Willebrand factor and factor VIII depends on cellular context: lessons from platelet-expressed factor VIII. Blood 2005 Jun 15;105(12):4674-6
Date
02/26/2005Pubmed ID
15731176DOI
10.1182/blood-2004-12-4701Scopus ID
2-s2.0-20444417088 (requires institutional sign-in at Scopus site) 32 CitationsAbstract
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.
Author List
Yarovoi H, Nurden AT, Montgomery RR, Nurden P, Poncz MAuthor
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
AnimalsAntigens
Blood Platelets
Cell Line
Exons
Factor VIII
Gene Deletion
Heterozygote
Homozygote
Humans
Immunohistochemistry
Macromolecular Substances
Mice
Mice, Transgenic
Microscopy, Electron
Platelet Activation
Protein Binding
Recombinant Proteins
von Willebrand Factor
