Platelet Adherence to Cultured Vascular Cells: Influence of Prostacyclin (PGI2)

Prostaglandin I2 (PGI2, prostacyclin) is released by cultures of venous endothelium from the human umbilical vein. Aspirin (ASA), an inhibitor of cyclooxygenase activity, prevents the release of PGI2 from the venous endothelium and causes an increase in platelet adherence in the presence of thrombin. If the PGI2 normally released from endothelium prevents the adherence of platelets, is the increased adherence of platelets to subendothelial components a result of decreased amounts of prostacyclin? Platelet adherence was quantitated using cultures of venous or arterial endothelium, venous or arterial smooth muscle, and arterial fibroblasts from the umbilical cord and cultures from a mouse hemangioendothelioma and mouse fibroblasts. 51Cr-labeled human platelets were incubated with the cell monolayers in the presence or absence of thrombin. PGI2 production was assessed by measuring 6-keto-prostaglandin F1α released into the supernatant. Thrombin induced release of 69 nM 6-keto-PGF1α with little adherence of platelets to venous endothelium; other cell monolayers released little or no 6-keto-PGF1α, and there was 55% or more platelet adherence. Exogenous PGI2 added to 1 mM ASA-treated cell monolayers and empty dishes decreased adherence significantly in all cases. A dose-response curve shows that monolayers of endothelial origin required little PGI2 to bring thrombin-induced adherence values to near control levels. Smooth muscle, arterial fibroblast, and mouse fibroblast monolayers or empty dishes, even with high concentrations of PGI2, still exhibited 25% or more platelet adherence in the presence of thrombin. PGI2 alone did not prevent thrombin-induced platelet adherence to the subendothelial components.