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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:258.)
© 2005 American Heart Association, Inc.

Thrombosis

Sulfatides Activate Platelets Through P-Selectin and Enhance Platelet and Platelet–Leukocyte Aggregation

Michael Merten; Christian Beythien; Kai Gutensohn; Peter Kühnl; Thomas Meinertz; Perumal Thiagarajan

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.

Correspondence to Dr Michael Merten, Division of Cardiology, Department of Internal Medicine, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. 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 disaggregation 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.

Sulfatides, sulfated glycosphingolipids, activated platelets via P-selectin as determined by an increase in activation of platelet GPIIb/IIIa and P-selectin. Therefore, sulfatides provide a positive feedback loop that can potentiate platelet aggregation. Furthermore, sulfatides aggregated washed platelets in a dose-dependent manner. In an ex vivo thrombosis model, sulfatides enhanced platelet and platelet–leukocyte aggregation.

Key Words: sulfatides • P-selectin • platelet aggregation • platelet–leukocyte aggregation

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