Abstract |
Thrombocytopenia and increased platelet clearance observed in von Willebrand disease-type 2B (VWD-2B) may be explained by platelet apoptosis triggered by the constitutive binding of VWF to its receptor, glycoprotein Ib (GPIb). Apoptosis was assessed in platelets from two patients with a severe VWD-2B mutation VWF/p.V1316M and from mice transiently expressing VWF/p.V1316M. We now report that the VWD-2B mutation VWF/p.V1316M which binds spontaneously to its receptor GPIbα does not induce apoptosis. In 2 unrelated patients (P1 and P2) exhibiting different VWF plasma levels (70% and 36%, respectively, compared with normal pooled human plasma given as 100%), inner transmembrane depolarization of mitochondria, characteristic of apoptotic events was undetectable in platelets, whether washed or in whole blood. No or a moderate phosphatidyl serine (PS) exposure as measured by annexin-V staining was observed for P1 and P2, respectively. Expression of pro-apoptotic proteins Bak and Bax, and caspase-3 activity were similar to control platelets. In the VWD-2B mouse model expressing high levels of mVWF/p.V1316M (423%), similar to what is found in inflammatory pathologies, no significant difference was observed between mice expressing mVWF/WT and mVWF/p.V1316M. These results strongly argue against apoptosis as a mechanism for the thrombocytopenia of severe VWD-2B exhibiting the VWF/p.V1316M mutation.
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Authors | Eliane Berrou, Alexandre Kauskot, Frédéric Adam, Amélie Harel, Paulette Legendre, Cécile Lavenu Bombled, Chantal Rothschild, Nicolas Prevost, Olivier D Christophe, Peter J Lenting, Cécile V Denis, Jean-Philippe Rosa, Marijke Bryckaert |
Journal | PloS one
(PLoS One)
Vol. 10
Issue 12
Pg. e0143896
( 2015)
ISSN: 1932-6203 [Electronic] United States |
PMID | 26645283
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Animals
- Apoptosis
(genetics)
- Female
- Humans
- Male
- Mice
- Mice, Inbred C57BL
- Mutation
- Thrombocytopenia
(genetics, pathology)
- von Willebrand Factor
(genetics)
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