Fibrinogenolysis and Fibrinolysis with Tissue Plasminogen Activator, Urokinase, Streptokinase-Activated Human Globulin, and Plasmin

Camiolo, Sarah M.; Thorsen, Sixtus; Astrup, Tage

doi:10.3181/00379727-138-35878

Cited by 173 publications

(76 citation statements)

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“…At higher concentrations of TPA, 25-100 U/ml plasma, the stimulatory effect of fibrin on complex generation was reduced to fourfold. In contrast to these observations with TPA, clotting plasma with Reptilase failed to enhance the generation of a2-plasmin inhibitor-plasmin complexes by UK, a finding that confirms and extends to plasma previous results utilizing purified systems (35)(36)(37)(38)(39).…”

Section: Discussioncontrasting

confidence: 54%

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Aspirin inhibits vascular plasminogen activator activity in vivo. Studies utilizing a new assay to quantify plasminogen activator activity.

Levin¹,

Harpel²,

Weil³

et al. 1984

J. Clin. Invest.

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A s bstract. Vascular or tissue-type plasminogen activator (TPA) is a key enzyme in physiologic fibrinolysis. To study the role of prostaglandins in modulating the synthesis and release of TPA in vivo, we prospectively studied the effect of aspirin (650 mg/d X 2) on TPA activity in 13 human subjects before and after 10 min of forearm venous occlusion. TPA activity was quantified by a newly developed enzyme-linked immunosorbent assay that both measures and differentiates between TPA and urokinase (UK)-like plasminogen activator activity. This assay is based on the observation that the concentration of a2-plasmin inhibitor-plasmin complexes in Reptilase-clotted plasma increases linearly in proportion to the amount of activator added. Resting TPA activity was higher in women than in men (0.56±0.59 vs. 0.15±0.1 1 U/ml, P = 0.049). Venous occlusion induced an eightfold rise in TPA activity in women (to 4.5 U/ml, P = 0.006) and a 15-fold rise in men (to 2.28 U/ ml, P = 0.004), whereas UK activity was not detected. Aspirin inhibited the rise in TPA activity after venous occlusion by 69% in men (P = 0.004) and 70% in women (P = 0.014). In contrast, aspirin had no effect on pre-or post-occlusion hematocrits or Factor VIII-related antigen levels. There was no correlation between plasma salicylate level and percentage inhibition ofTPA. Neither exogenous aspirin (0-1 ,ug/ml) nor salicylate (0-70 ug/ml) inhibited the generation of a2-plasmin inhibitor-plasmin complexes by exogenous TPA or interfered with the assay system. We conclude that aspirin may have an antifibrinolytic effect in man that has not been previously described.

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Section: Discussioncontrasting

confidence: 54%

“…Fibrin catalyzes the activation of plasminogen by TPA in purified systems (35)(36)(37)(38). The present studies show that fibrin also accelerates the TPA-induced generation of a2-plasmin inhibitor-plasmin complexes in plasma.…”

Section: Discussionmentioning

confidence: 56%

Aspirin inhibits vascular plasminogen activator activity in vivo. Studies utilizing a new assay to quantify plasminogen activator activity.

Levin¹,

Harpel²,

Weil³

et al. 1984

J. Clin. Invest.

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“…Authors in [29] reported that cultured bovine endothelial cells synthesized both u-PA and t-PA, while those in [30] found that only antibodies to t-PA, and not antibodies to u-PA, inhibits plasminogen activator activity in human endothelium in tissue sections, as measured by the fibrin overlay method described in [31]. The studies in [30], however, did not exclude that the endothelium still contained considerable amounts of u-PA, because the fibrin overlay method preferenti~ly may detect t-PA, as it is known that the activity of t-PA, in contrast to u-PA, is greatly enhanced by fibrin [32,33]. The present study shows that also on a molar basis the endothelial cells in the intact organism mainly contain t-PA and no demonstrable amounts of u-PA.…”

Section: Discussionmentioning

confidence: 99%

Human endothelial cells contain one type of plasminogen activator

Larsson²,

et al. 1984

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At least two types of animal plasminogen activating enzymes exist, differing in amino acid sequence, molecular mass and immunological reactivity: the urokinase‐type and the tissue‐type plasminogen activators. By affinity chromatography with monoclonal antibodies, we have purified the human activators of both types to homogeneity. Using immunocytochemistry with rabbit antibodies raised against these preparations, we now demonstrate that the plasminogen activator present in endothelium of veins and other blood vessels is of the tissue‐type. No urokinase‐type plasminogen activator immunoreactivity was detected in endothelial cells in the intact organism. These findings support the assumption that mobilization of plasmin for different purposes may involve different types of plasminogen activators, and that the plasminogen activator involved in thrombolysis is of the tissue‐type.

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“…It has previously been shown that activation of plasminogen by t-PA is strongly enhanced in the presence of fibrin [2 -41, while activation by urokinase is much less influenced by flbrin [2,5]. Using CNBrdigested fibrinogen (CNBr-Fg) as an alternative cofactor to solid-phase fibrin [6], kinetic analysis of the activation of Glu-plasminogen by t-PA has been performed under true equilibrium conditions, showing a 1800-fold increase of the catalytic efficiency (kcat/Km) of t-PA as compared to the absence of stimulator [7].…”

mentioning

confidence: 99%

Influence of cyanogen-bromide-digested fibrinogen on the kinetics of plasminogen activation by urokinase

1984

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The catalytic efficiency (kcat/Km) of hgh-molecular-mass urokinase for the activation of Glu-plasminogen is increased about 10-fold in the presence of CNBr-digested fibrinogen. This stimulation is similar to that observed with 6-aminohexanoic acid, and yields kinetic parameters comparable to those for the activation of Lysplasminogen by urokinase. The increase of the activation rate of Glu-plasminogen by urokinase in the presence of CNBr-Fg can thus be explained by a conformational change in the plasminogen molecule similar to that observed upon conversion of Glu-plasminogen to Lys-plasminogen and upon binding of 6-aminohexanoic acid to Glu-plasminogen. Stabilization of the Michaelis complex between urokinase and plasminogen by formation of a cyclic ternary complex with CNBr-Fg, which has been invoked to explain the dramatic stimulatory effect of CNBr-Fg on the activation of plasminogen by tissue-type plasminogen activator, does not appear to play a significant role in the increased activation rate.Urokinase and tissue-type plasminogen activator (t-PA) are two different plasminogen activators 111. It has previously been shown that activation of plasminogen by t-PA is strongly enhanced in the presence of fibrin [2 -41, while activation by urokinase is much less influenced by flbrin [2,5]. Using CNBrdigested fibrinogen (CNBr-Fg) as an alternative cofactor to solid-phase fibrin [6], kinetic analysis of the activation of Glu-plasminogen by t-PA has been performed under true equilibrium conditions, showing a 1800-fold increase of the catalytic efficiency (kcat/Km) of t-PA as compared to the absence of stimulator [7].In the present study we have investigated the influence of CNBr-Fg on the activation of Glu-plasminogen by highmolecular-mass urokinase. MATERIALS AND METHODS Proteins and reagents

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Fibrinogenolysis and Fibrinolysis with Tissue Plasminogen Activator, Urokinase, Streptokinase-Activated Human Globulin, and Plasmin

Cited by 173 publications

References 0 publications

Aspirin inhibits vascular plasminogen activator activity in vivo. Studies utilizing a new assay to quantify plasminogen activator activity.

Aspirin inhibits vascular plasminogen activator activity in vivo. Studies utilizing a new assay to quantify plasminogen activator activity.

Human endothelial cells contain one type of plasminogen activator

Influence of cyanogen-bromide-digested fibrinogen on the kinetics of plasminogen activation by urokinase

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