The involvement of the mitogen-activated protein kinase c-Jun NH2-terminal kinase-1 (JNK1) has never been investigated in hemostasis and thrombosis. Using two JNK inhibitors (SP600125 and 6o), we have demonstrated that JNK1 is involved in collagen-induced platelet aggregation dependent on ADP. In these conditions, JNK1 activation requires the coordinated signaling pathways of collagen receptors...

Platelet function testing (PFT), usually performed by techniques such as light transmission aggregometry (LTA), has traditionally been used to diagnose inherited qualitative and quantitative defects in platelet function, such as von Willebrand disease or Glanzmann thrombasthenia. With the increased use of antiplatelet agents to prevent arterial thrombosis and the interest in identifying patient...

From the initial description of platelets in 1882, their propensity to aggregate and to contribute to thrombosis was apparent. Indeed, excessive platelet aggregation is associated with myocardial infarction and other thrombotic diseases whereas Glanzmann thrombasthenia, in which platelet aggregation is reduced, is a bleeding syndrome. Over the last half of the 20th century, many investigators h...

The cytoadhesin family consists of platelet glycoprotein (GP) IIb-IIIa and the endothelial vitronectin receptor. The beta subunit (GP IIIa) of these complexes expresses the alloantigen Zwa (or PIA1). This alloantigen is not expressed by members of other integrin subfamilies. By using immunoprecipitation and immunoblot techniques, we found that the beta subunit of a heterodimer, expressed by cul...

Glanzmann thrombasthenia is an inherited bleeding disorder characterized by absence or dysfunction of the platelet integrin a IIb b 3 . Patient RM is a thrombasthenic variant whose platelets fail to aggregate in response to physiological agonists, despite the fact that they express abundant levels of a IIb b 3 on their surface. Binding of soluble fibrinogen or fibrinogen mimetic antibodies to R...

We studied the defect responsible for Glanzmann thrombasthenia in a patient whose platelets expressed < 5% of the normal amount of GPIIb-IIIa. Genetic and biochemical evidence indicated that the patient's GPIIIa genes were normal. However, DNA analysis revealed the patient homozygous for a G818-->A substitution in her GPIIb genes, resulting in a Gly273-->Asp substitution adjacent to the first G...

Integrin αIIbβ3 is indispensable for normal hemostasis, but its role for thrombopoiesis is still controversial. Recently, αIIb and β3 mutations have been identified in patients with congenital macrothrombocytopenia. We analyzed three unrelated Japanese families with congenital macrothrombocytopenia. Expression and activation state of αIIbβ3 in platelets was examined by flow cytometry and immuno...