Regulation of fibrinolytic activity of neutrophil leukocyte elastase, plasmin, and miniplasmin by plasma protease inhibitors.

Kolev, Krasimir; Léránt, István; Tenekejiev, Kiril; Machovich, Raymund

doi:10.1016/s0021-9258(17)32515-2

Cited by 75 publications

(19 citation statements)

References 28 publications

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“…The effects of A1AT are not obvious until both A1AT and A2M are removed. In this system, A1AT appears to play a role redundant to A2M except much weaker, due to its much slower binding to plasmin [22]. When A2M is removed from the system (Fig 5C), uPA mediated fibrinolysis becomes much more apparent.…”

Section: Upa Mediated Fibrinolysismentioning

confidence: 86%

Computational model of tranexamic acid on urokinase mediated fibrinolysis

Orfeo

Moore

et al. 2020

PLoS ONE

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Understanding the coagulation process is critical to developing treatments for trauma and coagulopathies. Clinical studies on tranexamic acid (TXA) have resulted in mixed reports on its efficacy in improving outcomes in trauma patients. The largest study, CRASH-2, reported that TXA improved outcomes in patients who received treatment prior to 3 hours after the injury, but worsened outcomes in patients who received treatment after 3 hours. No consensus has been reached about the mechanism behind the duality of these results. In this paper we use a computational model for coagulation and fibrinolysis to propose that deficiencies or depletions of key anti-fibrinolytic proteins, specifically antiplasmin, a1-antitrypsin and a2-macroglobulin, can lead to worsened outcomes through urokinase-mediated hyperfibrinolysis.

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Section: Upa Mediated Fibrinolysismentioning

confidence: 86%

Computational model of tranexamic acid on urokinase mediated fibrinolysis

Orfeo

Moore

et al. 2020

PLoS ONE

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“…Because plasmin is the major fibrinolytic enzyme, it is possible that reduced plasmin activity in leg ulcers could contribute to fibrosis, a very common feature of leg ulcers (Falanga, 1993). Neutrophil elastase also has fibrinolytic activity (Kolev et al, 1994), but its role in fibrinolysis during wound healing has not been established.…”

Section: Discussionmentioning

confidence: 99%

Wound Fluid from Venous Leg Ulcers Degrades Plasminogen and Reduces Plasmin Generation by Keratinocytes

Hoffman

Starkey

Coad

1998

Journal of Investigative Dermatology

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Plasminogen, the pro-enzyme of plasmin, aids various processes essential for normal, acute wound healing, such as fibrinolysis and cell migration. We have investigated if plasminogen is available to perform these functions in chronic wounds such as venous leg ulcers. We report that plasminogen is degraded by fluid from venous leg ulcers to a number of fragments, including kringle domains 1-3, an angiostatin-related protein. The enzyme responsible was inhibited by the serine protease inhibitor phenyl-methylsulfonyl fluoride, but was not inhibited by alpha1-anti-trypsin, an inhibitor of neutrophil elastase, by alpha2-anti-plasmin, an inhibitor of plasmin, or by the matrix metalloprotease inhibitor 1,10 phenanthroline. Plasminogen degraded by wound fluid was a weaker substrate than intact plasminogen for plasmin generation by the keratinocyte cell line HaCaT. These results suggest that serine protease activity in leg ulcer fluid degrades plasminogen and support the hypothesis that keratinocyte migration may be impaired in leg ulcers because of a reduced availability of intact plasminogen for plasmin generation.

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“…Plasmin (PL) was obtained by activation of plasminogen from bovine plasma (PLG, lyophilized powder, Sigma-Aldrich) by urokinase (uPA) from human urine (EMD Millipore) using 1 mg plasminogen : 35 000 U urokinase ratio based on modified literature protocols [22][23]. After activation, the nominally 1 µM concentration of the PL was exactly determined by measuring the absorbance change at 405 nm wavelength in 60 seconds of a series of Spectrozyme-PL (H-Dnorleucyl-hexahydrotyrosyl-lysine-p-nitroanilide, Sekisui Diagnostics, LLC, USA) solutions prepared in Tris (2-amino-2-(hydroxymethyl)propane-1,3-diol) buffer (20 mM Tris + 150 mM NaCl at pH = 7.4), digested by the active enzyme, as described in [24]. The active plasmin concentration was obtained as a parameter, by nonlinear fitting of the Michaelis-Menten equation to the obtained dA/dt (rate of absorbance change) vs. c S (Spectrozyme-PL concentration) data points.…”

Section: Reagents and β-Casein Layer Preparationmentioning

confidence: 99%

Casein probe–based fast plasmin determination in the picomolar range by an ultra-high frequency acoustic wave biosensor

Románszki

Tatarko

Jiao

et al. 2018

Sensors and Actuators B: Chemical

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Detection of residual plasmin activity in milk represents a difficult challenge for the dairy industry. Conventional methods are either too expensive or incapable of providing enough data from UHT treated milk. Acoustic wave-based biosensors operated in the thickness shear mode (TSM) showed potential for the detection of proteolysis of β-casein, a milk protein by protease plasmin. An ultra-high frequency device, the electromagnetic piezoelectric acoustic sensor (EMPAS), designed to enhance the sensitivity of TSM, was tested for detection of plasmin at low concentrations. β-casein layers immobilised on the hydrophilic or hydrophobized surfaces of EMPAS quartz discs served as substrate for the enzyme. In contrast with conventional TSM devices, the shearing oscillations in EMPAS are induced contactless, by a magnetic coil located 30 μm below the quartz crystal. This configuration allows the registration of unusually high harmonics (up to the 49 th -53 rd ), thus enhancing the sensitivity of detection. On both surface types, the adsorbed βcasein mass and the stability of the layer was compared, with the result that hydrophobic surfaces provide superior conditions for immobilisation than the hydrophilic case. Consequent proteolysis measurements of these substrate layers were carried out in a broad plasmin concentration range (32 pM -10 nM) in flow mode. Initial reaction rates measured at different enzyme concentrations have been used to construct a calibration curve based on an inverse Michaelis-Menten type equation. The sensitivity of the EMPAS allowed measurements of as low as 32 pM concentration of plasmin, reaching (and often exceeding) levels comparable to state of the art techniques like ELISA. The presented method however, unlike ELISA, is effective on a timescale of minutes.

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Regulation of fibrinolytic activity of neutrophil leukocyte elastase, plasmin, and miniplasmin by plasma protease inhibitors.

Cited by 75 publications

References 28 publications

Computational model of tranexamic acid on urokinase mediated fibrinolysis

Computational model of tranexamic acid on urokinase mediated fibrinolysis

Wound Fluid from Venous Leg Ulcers Degrades Plasminogen and Reduces Plasmin Generation by Keratinocytes

Casein probe–based fast plasmin determination in the picomolar range by an ultra-high frequency acoustic wave biosensor

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