on November 4, 2004
Published online before print November 4, 2004, doi: 10.1161/01.ATV.0000149675.83552.83
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Submitted on April 26, 2004
Accepted on October 15, 2004
Sulfatides Activate Platelets Through P-Selectin and Enhance Platelet and Platelet-Leukocyte Aggregation
Michael Merten *;
From the Division of Cardiology (M.M., T.M.) and the Department of Internal Medicine and Department of Transfusion Medicine (K.G., P.K.), University Hospital Hamburg-Eppendorf, Hamburg, Germany; the Division of Cardiology (C.B.), Department of Internal Medicine, University Hospital Rostock, Germany; and the Department of Pathology and Medicine (P.T.), Baylor College of Medicine, Houston, Tex.
* To whom correspondence should be addressed. E-mail: michael_merten{at}yahoo.com.
Objective--Sulfatides are sulfated glycosphingolipids present on the surface of a variety of cells; however, their exact physiological function is not known. Recently, we have shown that the inhibition of sulfatide-P-selectin interactions leads to de-aggregation of platelet aggregates.
Methods and Results--In this study, we show that sulfatides activated platelets as they increased activation of GPIIb/IIIa (PAC-1 epitope) and expression of P-selectin on the platelet surface. Furthermore, sulfatides aggregated washed platelets in a dose-dependent manner and enhanced platelet aggregation in platelet-rich plasma. Previous activation of platelets was necessary for this effect. Monoclonal anti-P-selectin antibodies inhibited not only sulfatide-induced PAC-1 binding to platelets but also sulfatide-induced platelet aggregation, suggesting that sulfatides activate platelet GPIIb/IIIa via signaling through P-selectin. The proaggegatory effect of sulfatides was also observed in an ex vivo thrombosis model using whole blood and pulsatile flow at 37°C. In this model, sulfatides significantly enhanced platelet aggregation and the formation of platelet-leukocyte aggregates.
Conclusions--We show that sulfatide-P-selectin interactions lead to subsequent platelet activation and P-selectin expression, forming a positive feedback loop that can potentiate formation of stable platelet aggregates. In addition, sulfatides enhance the aggregation of platelet-leukocyte aggregates. These mechanisms may play a significant role in hemostasis and thrombosis.
Key words: sulfatides • P-selectin • platelet aggregation • platelet-leukocyte aggregation
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