on December 15, 2005
Published online before print December 15, 2005, doi: 10.1161/01.ATV.0000200391.70818.a9
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Submitted on July 4, 2005
Accepted on November 29, 2005
Glycoprotein Ib
-Mediated Platelet Adhesion and Aggregation to Immobilized Thrombin Under Conditions of Flow
Cees Weeterings ;
From the Thrombosis and Haemostasis Laboratory (C.W., J.A., P.G.d.G., T.L.), Department of Haematology, University Medical Centre Utrecht, the Netherlands; the Institute of Biomembranes (C.W., P.G.d.G., T.L.), Utrecht University, Utrecht, the Netherlands; and the Division of Hematology (T.M.), Department of Medicine, Stanford University School of Medicine, Stanford, Calif.
* To whom correspondence should be addressed. E-mail: j.a.lisman{at}azu.nl.
Objectives--Thrombin interacts with platelets via the protease-activated receptors (PARs) 1 and 4, and via glycoprotein Ib
(GPIb). Recently, it was shown that platelets are able to adhere to immobilized thrombin under static conditions via GPIb.
Methods and Results--Here, we show that platelets are also able to adhere to and form stable aggregates on immobilized thrombin under conditions of flow. Adhesion and aggregation to thrombin was dependent on the interaction with GPIb, as addition of glycocalicin or an antibody blocking the interaction between thrombin and GPIb inhibited platelet adhesion. Additionally, platelet adhesion to recombinant thrombin mutants, which are unable to bind GPIb, was severely suppressed. Furthermore, platelet adhesion to thrombin was dependent on activation of PARs, and partly on granule secretion and thromboxane-A2 synthesis. Immobilization of thrombin on a fibrin network resulted in substantially increased adhesion compared with fibrin alone. The adhesion to fibrin alone was completely abolished by addition of dRGDW, whereas fibrin-bound thrombin still showed substantial platelet adhesion in the presence of dRGDW, indicating that fibrin-bound thrombin is able to directly capture platelets under flow.
Conclusion--These results indicate that platelets are able to adhere to thrombin under flow conditions, which is dependent on the interaction with GPIb.
Key words: thrombin • platelet • fibrin • GPIb
•
flow conditions
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