We have identified a novel cellular action of thrombin on cultured rat adrenal medullary endothelial cells (RAMEC). Five-minute incubation of RAMEC with physiological concentrations of thrombin (<1 U/ml) caused within 3 h an increase in the basolateral deposition of the extracellular matrix (ECM) proteins fibronectin, laminin, and collagens IV and I, concomitant with a corresponding decrease in...

Thrombin, in addition to its central role in hemostasis, possesses diverse cellular bioregulatory functions implicated in wound healing, inflammation, and atherosclerosis. In the present study we demonstrate that thrombin molecules modified either at the procoagulant or catalytic sites induce endothelial cell (EC) adhesion, spreading, and cytoskeletal reorganization. The most potent adhesive th...

BACKGROUND The degree to which antithrombotic drugs suppress thrombin generation is unknown. Because hirudin, unlike antithrombin III, binds intravascular thrombin rapidly and selectively to yield a circulating inactive complex of 3- to 4-hour half-life, we used intravenous hirudin in humans to investigate the course of thrombin generation during and early after anticoagulation with this potent...

In closed system models of fibrin formation, exosite-mediated thrombin binding to fibrin contributes to clot stability and is resistant to inhibition by antithrombin/heparin while still susceptible to small, active-site inhibitors. Each molecule of fibrin can bind ∼1.6 thrombin molecules at low-affinity binding sites (Kd = 2.8 μM) and ∼0.3 molecules of thrombin at high-affinity binding sites (K...

Stress-induced activation of haemostasis may be involved in the triggering of acute coronary syndromes. We compared the effects of mental stress, dynamic exercise and adrenaline infusion on platelet sensitivity to thrombin using flow-cytometric analysis of platelet fibrinogen binding in whole blood, and platelet aggregability using filtragometry ex vivo, in healthy volunteers. Furthermore, we a...

Neutrophil cathepsin G and thrombin, the only platelet agonists that are proteases, exhibit a mandatory requirement for catalytic activity to induce platelet aggregation and signal transduction. The thrombin receptor is a G-protein-coupled receptor which undergoes proteolysis to generate a tethered ligand that causes self-activation. Since cathepsin G strongly resembles thrombin in its ability ...

A mutant prothrombin, designated prothrombin Tokushima, was purified from plasma of a proband with 12% of normal plasma clotting activity and 42% of normal prothrombin antigen. The purified preparation gave a single band with the same mobility as that of "prothrombin" by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The factor Xa-catalyzed proteolysis of prothrombin Toku...

Single-stranded DNA molecules containing a 15-nucleotide consensus sequence have been reported to inhibit thrombin activity. The mechanism of the inhibition was studied using a consensus 15-mer oligonucleotide and two recombinant mutant thrombins: the anion-binding exosite mutant thrombin R70E, and thrombin K154A, in which the mutation was located in a surface loop outside of the exosite. The c...

Acute and chronic interstitial lung diseases are accompanied by evidence of inflammation and vascular injury. Thrombin activity in bronchoalveolar lavage fluid from such conditions is often increased, as well as interleukin (IL)-8. We observed that conditioned medium from lung fibroblasts exposed to thrombin has chemotactic activity for polymorphonuclear cells, and that this activity can be abo...