Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates

OBJECTIVES We investigated the role of P-selectin in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates. BACKGROUND Plaque rupture followed by thrombus formation is a fundamental pathophysiology of acute coronary syndromes. Although the adhesive interaction between platelets and leukocytes via P-selectin is known to mediate platelet-rich thrombi, the true function of P-selectin in thrombus formation in vivo is unknown. METHODS In wild-type (P+/+) and P-selectin-deficient (P-/- ) mice with ferric chloride (FeCl3)-induced carotid arterial thrombosis model, we measured in vivo platelet P-selectin expression and adenosine diphosphate (ADP)-induced ex vivo platelet aggregation. We also measured ex vivo ADP-induced whole blood aggregations and their size distribution by flow cytometry. RESULTS Time to thrombotic occlusion was longer in P-/- mice than in P (+/+) mice. Spontaneous reflow after total thrombotic occlusion was observed in 8 of 10 P (-/-) mice but not in any P+/+ mice. ADP-induced ex vivo platelet aggregation was not different between the two groups. However, ADP-induced ex vivo whole blood aggregation was inhibited in P-/- mice compared to P+/+ mice. FeCl3, application increased in vivo expressions of platelet P-selectin in P+/+ mice but not in P-/- mice. The number of leukocytes within thrombi was less in P-/- mice than in P+/+ mice. In flow cytometric analysis of size distribution of ADPinduced whole blood aggregates, the number of large aggregates was less in P-/- mice than in P+/+ mice. Using platelet and leukocyte fluorescence makers, the large aggregates were confirmed as platelet-leukocyte aggregates. CONCLUSIONS Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates.