Trypsin-activated pig plasmin and human plasmin activated by streptokinase (SK) caused aggregation of a suspension of washed platelets from human, rabbit, or pig blood. The platelet aggregation was reversible, but it was accompanied by a significant release of adenine nucleotides, serotonin, and platelet fibrinogen. Platelet fibrinogen was eventually digested. The effect of plasmin on platelets...

Extracellular manipulation of protein disulfide bonds has been implied in diverse biological processes, including penetration of viruses and endotoxin into cells and activation of certain cytokine receptors. We now demonstrate reduction of one or more disulfide bonds in the serine proteinase, plasmin, by a reductase secreted by Chinese hamster ovary or HT1080 cells. Reduction of plasmin disulfi...

The rate of diffusion of a protein in solution from a source in agar gel is, within limits, proportional to its original concentration (Ouchterlony, 1949). When plasminogen in biological fluids is allowed to diffuse from a source in agar/fibrinogen gel for a given time, the distance diffused can be ascertained by activation of the plasminogen to plasmin by streptokinase after diffusion has take...

Semi-synthetic, proteolytically degradable polymer hydrogels have proven effective as scaffolds to augment bone and skin regeneration in animals. However, high costs due to expensive peptide building blocks pose a significant hurdle towards broad clinical usage of these materials. Here we demonstrate that tri-amino acid peptides bearing lysine (or arginine), flanked by two cysteine residues for...

Streptokinase (SK) binds to plasminogen (Pg) to form a complex that converts substrate Pg to plasmin. Residues 1-59 of SK regulate its capacity to induce an active site in bound Pg by a nonproteolytic mechanism and to activate substrate Pg in a fibrin-independent manner. We analyzed 24 SK mutants to better define the functional properties of SK-(1-59). Mutations within the alphabeta1 strand (re...

In vivo plasminogen responses to various stimuli were studied. Plasminogen-(125)I was prepared and used first for metabolic studies of plasminogen in control dogs. The average results were: the plasma plasminogen, 29.3+/-4.1 (SD) mg/kg; the interstitial plasminogen, 8.79+/-4.47 (SD) mg/kg; the half-life of plasma plasminogen-(125)I, 2.81+/-0.24 (SD) days; the fractional direct catabolic rate of...

The objective of this study was to determine the effects of stage of lactation (SOL) and time of year on plasmin-derived proteolytic activity in the milk of pasture-fed dairy cows in New Zealand. Four herds of 20 Friesian cows were used, one herd calving in each of January, April, July and October. Cows grazed ryegrass/white clover pasture only, except during June (winter) when all cows receive...

Human antiplasmin, the fast-acting plasmin inhibitor in plasma, was purified to homogeneity and labeled with 125I. This material, which was indistinguishable from antiplasmin in plasma with respect to several physicochemical and functional properties, was injected intravenously and its turnover measured in control subjects and in patients undergoing thrombolytic therapy. In eight control subjec...

Bee venom is a rich source of pharmacologically active substances. In this study, we identified a bumblebee (Bombus ignitus) venom Kunitz-type serine protease inhibitor (Bi-KTI) that acts as a plasmin inhibitor. Bi-KTI showed no detectable inhibitory effect on factor Xa, thrombin, or tissue plasminogen activator. In contrast, Bi-KTI strongly inhibited plasmin, indicating that it acts as an anti...