Kinetics of platelet P-selectin mobilization: Concurrent surface expression and release induced by thrombin or PMA, and inhibition by the NO donor SNAP
Pa. Whiss et al., Kinetics of platelet P-selectin mobilization: Concurrent surface expression and release induced by thrombin or PMA, and inhibition by the NO donor SNAP, CELL AD COM, 6(4), 1998, pp. 289-300
Activated platelets and endothelium surface express the cell adhesion molec
ule P-selectin (CD62P), which plays an important role in mediating interact
ions with leukocytes, Increased levels of a functional soluble form of P-se
lectin (sP-selectin) have been reported in several pathological states but
it is not clear whether this circulating sP-selectin originates from platel
ets and/or endothelial cells. Here we describe the concurrent kinetics of i
ntracellular storage, surface expression and release of platelet P-selectin
induced by thrombin or the protein kinase C activator PMA. Platelet activa
tion with submaximal concentrations of thrombin (0.1 U/ml) resulted in a ra
pid decrease of intracellular P-selectin. This decrease of intracellular P-
selectin concurred with a gradual increase of surface expression and an ini
tial increase of sP-selectin. Our results indicate that intracellular store
s of P-selectin were only partly mobilized upon activation with submaximal
concentrations of thrombin. A high concentration of thrombin (1.0 U/ml) ind
uced a rapid and nearly total decrease of intracellular stores and a more p
ronounced, but transient, increase of surface expression. The release of P-
selectin was fast and occurred during the initial activation phase. The NO
donor SNAP inhibited both surface expression and release of platelet P-sele
ctin in a similar manner. PMA (0.1-1.0 mu M) mediated a more slow, gradual
and sustained surface expression and release of P-selectin than thrombin. T
hus, surface expression and release of platelet P-selectin show different k
inetics depending on the mode of activation.