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Blood, Vol. 94 No. 12 (December 15), 1999:
pp. 4112-4121
Glycoprotein V-Deficient Platelets Have Undiminished Thrombin
Responsiveness and Do Not Exhibit a Bernard-Soulier Phenotype
Mark L. Kahn,
Thomas G. Diacovo,
Dorothy F. Bainton,
Francois Lanza,
JoAnn Trejo, and
Shaun R. Coughlin
From the Department of Medicine, University of Pennsylvania,
Philadelphia, PA; the Department of Pediatrics and Pathology,
Washington University, St Louis, MO; the Department of Pathology,
Cardiovascular Research Institute, and Departments of Medicine and
Cellular and Molecular Pharmacology, University of California, San
Francisco, CA; and INSERM U.311, Strasbourg, France.
Adhesion of platelets to extracellular matrix via von Willebrand
factor (vWF) and activation of platelets by thrombin are critical steps
in hemostasis. Glycoprotein (GP) V is a component of the GPIb-V-IX
complex, the platelet receptor for vWF. GPV is also cleaved by
thrombin. Deficiency of GPIb or GPIX results in Bernard-Soulier
syndrome (BSS), a bleeding disorder in which platelets are giant and
have multiple functional defects. Whether GPV-deficiency might also
cause BSS is unknown as are the roles of GPV in platelet-vWF interaction and thrombin signaling. We report that GPV-deficient mice
developed normally, had no evidence of spontaneous bleeding, and had
tail bleeding times that were not prolonged compared with wild-type
mice. GPV-deficient platelets were normal in size and structure as
assessed by flow cytometry and electron microscopy. GPV-deficient and
wild-type platelets were indistinguishable in botrocetin-mediated
platelet agglutination and in their ability to adhere to mouse vWF A1
domain. Platelet aggregation and ATP secretion in response to low and
high concentrations of thrombin were not decreased in GPV-deficient
platelets compared with wild-type. Our results show that (1) GPV is not
necessary for GPIb expression and function in platelets and that GPV
deficiency is not likely to be a cause of human BSS and (2) GPV is not
necessary for robust thrombin signaling. Whether redundancy accounts
for the lack of phenotype of GPV-deficiency or whether GPV serves
subtle or as yet unprobed functions in platelets or other cells remains
to be determined.
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