TY - JOUR
T1 - Abnormal VWF modifies megakaryocytopoiesis
T2 - Studies of platelets and megakaryocyte cultures from patients with von Willebrand disease type 2B
AU - Nurden, Paquita
AU - Gobbi, Giuliana
AU - Nurden, Alan
AU - Enouf, Jocelyne
AU - Youlyouz-Marfak, Ibtissam
AU - Carubbi, Cecilia
AU - La Marca, Silvia
AU - Punzo, Margherita
AU - Baronciani, Luciano
AU - De Marco, Luigi
AU - Vitale, Marco
AU - Federici, Augusto B.
PY - 2010/4/1
Y1 - 2010/4/1
N2 - von Willebrand factor (VWF) is an essential mediator of platelet adhesion to the vessel wall, but little is known about its role in megakaryocytopoiesis. VWF and its platelet receptor, glycoprotein Ibα (GPIbα), are both expressed during megakaryocyte (MK) maturation. This study was designed to evaluate whether the enhanced VWF-GPIbα interactions typical of patients with von Willebrand disease type 2B (VWD2B) modify platelet production. Platelets from 9 patients with VWD2B with 7 different gain-of-function mutations were examined by electron microscopy (EM) and immunofluorescence labeling. For the patients with VWD2B, EM characteristically showed variable numbers of structurally abnormal giant platelets, sometimes in agglutinates. Cultures of MKs from controls performed with or without purified VWF confirmed a positive influence of VWF on platelet production with specific inhibition by an antibody blocking VWF binding to GPIbα. VWD2B MK cultures examined by EM showed a disorganized demarcation membrane system and abnormal granule distribution. They produced platelets with structural abnormalities typical of VWD2B. Confocal examination of MK revealed limited extension of pseudopods with few large proplatelets. These results confirm that megakaryocytopoiesis is modified by the enhanced VWF-GPIbα interactions. These data obtained for controls and patients with VWD2B suggest a novel regulatory role of VWF-GPIbα interactions in platelet production.
AB - von Willebrand factor (VWF) is an essential mediator of platelet adhesion to the vessel wall, but little is known about its role in megakaryocytopoiesis. VWF and its platelet receptor, glycoprotein Ibα (GPIbα), are both expressed during megakaryocyte (MK) maturation. This study was designed to evaluate whether the enhanced VWF-GPIbα interactions typical of patients with von Willebrand disease type 2B (VWD2B) modify platelet production. Platelets from 9 patients with VWD2B with 7 different gain-of-function mutations were examined by electron microscopy (EM) and immunofluorescence labeling. For the patients with VWD2B, EM characteristically showed variable numbers of structurally abnormal giant platelets, sometimes in agglutinates. Cultures of MKs from controls performed with or without purified VWF confirmed a positive influence of VWF on platelet production with specific inhibition by an antibody blocking VWF binding to GPIbα. VWD2B MK cultures examined by EM showed a disorganized demarcation membrane system and abnormal granule distribution. They produced platelets with structural abnormalities typical of VWD2B. Confocal examination of MK revealed limited extension of pseudopods with few large proplatelets. These results confirm that megakaryocytopoiesis is modified by the enhanced VWF-GPIbα interactions. These data obtained for controls and patients with VWD2B suggest a novel regulatory role of VWF-GPIbα interactions in platelet production.
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U2 - 10.1182/blood-2009-07-231886
DO - 10.1182/blood-2009-07-231886
M3 - Article
C2 - 20118404
AN - SCOPUS:77950967181
VL - 115
SP - 2649
EP - 2656
JO - Blood
JF - Blood
SN - 0006-4971
IS - 13
ER -