Von Willebrand factor (vWF) is a large glycoprotein which plays a central role in thrombus formation and blood clotting. The type IIB variant of vWF is characterized by an abnormally high affinity for the platelet receptor GPIb. Type IIB vWF purified from plasma and added to a platelet suspension induced a rapid, dose-dependent (1.2-9 μg/ml) increase in the cytosolic Ca2+ concentration. ATP secretion and platelet aggregation also occurred with type IIB vWF concentrations higher than about 5 μg/ml, which corresponds to the original plasmatic level. The IIB vWF-evoked (3 μg/ml) cytosolic Ca2+ increase was negligibly affected by ADP scavengers or protein kinase C inhibitors; it was drastically reduced by EGTA, La3+, Ni2+ or acetylsalicylate and abolished by the phospholipase A2 inhibitors ONO-RS-082 or oleolyloxyethyl-phosphocholine. Platelet exposure to IIB vWF caused arachidonic acid release, thromboxane B2 and inositoltrisphosphate formation. LJIB1, a monoclonal antibody against GPIb, completely suppressed all platelet responses, whereas LJCP8, an antibody against the receptor GPIIb-IIIa (αIIbβ3 integrin), or the tetrapeptide RGDS, caused a complete inhibition of the aggregation but a partial inhibition of the activation-linked parameters. It is concluded that type IIB vWF-binding to GPIb induces phospholipase A2 activation, arachidonic acid release and GPIIb-IIIa dependent cellular Ca2+ influx. These events may lead to platelet secretion and aggregation.

Type IIB von Willebrand Factor induces phospholipase A2 activation and cytosolic Ca2+ increase in platelets

CASONATO, SANDRA;PONTARA, ELENA;DALLA VIA, LISA;GIROLAMI, ANTONIO;DEANA, RENZO
1995

Abstract

Von Willebrand factor (vWF) is a large glycoprotein which plays a central role in thrombus formation and blood clotting. The type IIB variant of vWF is characterized by an abnormally high affinity for the platelet receptor GPIb. Type IIB vWF purified from plasma and added to a platelet suspension induced a rapid, dose-dependent (1.2-9 μg/ml) increase in the cytosolic Ca2+ concentration. ATP secretion and platelet aggregation also occurred with type IIB vWF concentrations higher than about 5 μg/ml, which corresponds to the original plasmatic level. The IIB vWF-evoked (3 μg/ml) cytosolic Ca2+ increase was negligibly affected by ADP scavengers or protein kinase C inhibitors; it was drastically reduced by EGTA, La3+, Ni2+ or acetylsalicylate and abolished by the phospholipase A2 inhibitors ONO-RS-082 or oleolyloxyethyl-phosphocholine. Platelet exposure to IIB vWF caused arachidonic acid release, thromboxane B2 and inositoltrisphosphate formation. LJIB1, a monoclonal antibody against GPIb, completely suppressed all platelet responses, whereas LJCP8, an antibody against the receptor GPIIb-IIIa (αIIbβ3 integrin), or the tetrapeptide RGDS, caused a complete inhibition of the aggregation but a partial inhibition of the activation-linked parameters. It is concluded that type IIB vWF-binding to GPIb induces phospholipase A2 activation, arachidonic acid release and GPIIb-IIIa dependent cellular Ca2+ influx. These events may lead to platelet secretion and aggregation.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/2484898
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