Role for sulfatides in platelet aggregation.
BACKGROUND
Sulfatides are sulfated glycosphingolipids present on the surface of oligodendrocytes, renal tubular cells, and certain tumor cells. They appear to be involved in nerve conduction and cell adhesion, but their precise physiological function is not known.


RESULTS
Here, we show a novel role for sulfatides as a major ligand for P-selectin in platelet adhesion and aggregation. Sulfatides are expressed on the platelet surface, and platelets expressing sulfatides adhere to P-selectin. Both sulfatide micelles and sulfatide-binding recombinant malaria circumsporozoite protein (MCSP) inhibit this adhesion. In parallel, platelets and CHO cells expressing P-selectin adhere to sulfatides, and anti-P-selectin antibodies inhibit this adhesion. Furthermore, both anti-P-selectin antibodies and sulfatide antagonist MCSP significantly reverse platelet aggregation induced by ADP, collagen, or thrombin receptor-activating peptide, suggesting that sulfatide-P-selectin interactions are necessary for the formation of stable platelet aggregates.


CONCLUSIONS
These results show that sulfatide interactions with P-selectin are important in platelet adhesion and platelet aggregation. The sulfatide interactions with P-selectin stabilize platelet aggregates, representing a new mechanism of platelet aggregation that may play a significant role in hemostasis and thrombosis.
Merten
M
M
Division of Cardiology, Department of Internal Medicine, University of Texas-Houston Medical School, Houston, TX, USA.
Thiagarajan
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects; D006224:Cricetinae; D005340:Fibrinogen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D015800:Protozoan Proteins / Q000494:pharmacology; D013433:Sulfoglycosphingolipids / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D019007:P-Selectin; D015800:Protozoan Proteins; D013433:Sulfoglycosphingolipids; C041595:circumsporozoite protein, Protozoan; D005340:Fibrinogen