| Recent studies demonstrated a role for annexin II (A2) and its ligand p11 in fibrinolysis. Since thrombin is a potent cell modulator obligately produced at the site of clot formation, the hypothesis was addressed that thrombin regulates fibrinolysis by increasing cell surface A2 and p11. Immunofluorescence and biotinylation established that thrombin significantly increases both on human umbilical vein endothelial cell (HUVEC) and human foreskin fibroblast surfaces. Intracellular antigenic analyses revealed increased p11 but unchanged A2, suggesting that transbilayer trafficking of A2 is controlled by p11. The thrombin receptor activating peptide similarly affected cells indicating signaling through protease activated receptor 1. A direct effect on fibrinolysis was shown by observations of increased plasminogen binding to HUVEC that was inhibited by anti-p11 antibody, and activation of plasminogen by tissue plasminogen activator. These data suggest a novel link between thrombin and fibrinolysis, and other processes that may involve A2, such as cytomegalovirus infection. |
