Kaur, Jaswinder, Richard C. Woodman, and Paul Kubes. P38 MAPK: critical molecule in thrombin-induced NFB-dependent leukocyte recruitment. Am J Physiol Heart Circ Physiol 284: H1095–H1103, 2003. First published December 27, 2002; 10.1152/ajpheart.00016.2002.—Thrombin-stimulated endothelium synthesizes numerous adhesion molecules to recruit leukocytes; however, it is unknown which intracellular p...

The heparin-enhanced antithrombin III/thrombin reaction was studied under a variety of conditions designed to determine the validity of kinetic models for the mechanism of action of heparin. The observed second order rate constant k& values for thrombin inhibition by antithrombin I11 were determined as a function of heparin concentration in the presence and absence of varying amounts of active ...

The activation of membrane-bound phospholipase D (PLD) resulting in the generation of phosphatidic acid (PA) is increasingly recognized as an integral event in the initiation of a variety of cellular responses. We explored whether alpha-thrombin is a physiologic agonist for PLD activation in human umbilical vein endothelial cells (HUVEC). HUVEC monolayers were labeled with [32Pi] and PLD activi...

BACKGROUND The contact phase of coagulation is of physiologic/pathophysiologic importance, whenever unphysiologic polynegative substances such as cell fragments (microparticles) get in contact with blood. There are several clinically used inhibitors of intrinsic thrombin generation. Here the inhibitory concentrations 50% (IC50) of these anticoagulants are measured by the highly specific thrombi...

a-Thrombin derivatives obtained either by site-specific modification at lysyl residues (phosphopyridoxylated) or by limited trypsinolysis (yT-thrombin) were compared to correlate structural modifications with the functional reactivity toward fibrin(ogen) and heparin. a-Thrombin phosphopyridoxylated in the absence of heparin (unprotected) showed approximately 2 mol of label incorporated/mol of t...

Depolymerized holothurian glycosaminoglycan (DHG) is a fucosylated chondroitin sulfate with antithrombin-independent antithrombotic properties. Heparin cofactor II (HCII)-dependent and -independent mechanisms for DHG inhibition of plasma thrombin generation were evaluated. When thrombin generation was initiated with 0.2 pM tissue factor (TF), the half maximal effective concentration (EC(50)) fo...

We compared concentrations of antithrombin III (AT-III) in plasma, as determined by an immunological method and by a functional thrombin inhibition method, in the presence of heparin in 160 blood samples from Type I diabetics. Although the correlation was highly significant (P less than 0.001) between the results obtained by the two methods, our data demonstrated that results by the thrombin in...

Development of inhibitory antibodies to coagulation factor VIII (fVIII) is the primary obstacle to the treatment of hemophilia A in the developed world. This adverse reaction occurs in 20-30% of persons with severe hemophilia A treated with fVIII-replacement products and is characterized by the development of a humoral and neutralizing immune response to fVIII. Patients with inhibitory anti-fVI...

Abstract The maintenance of hemostasis to ensure vascular integrity is dependent upon the rapid conversion zymogen species coagulation cascade their enzymatically active forms. This process culminates in generation serine protease thrombin and polymerization fibrin prevent leak at sites endothelial cell injury or loss cellular junctions. Thrombin can be initiated by extrinsic pathway through ex...