Faculty Opinions recommendation of Polyphosphate colocalizes with factor XII on platelet-bound fibrin and augments its plasminogen activator activity.

2016 ◽  
Author(s):  
Lindsey A Miles
Keyword(s):  
Plasminogen Activator ◽  
Factor Xii ◽  
Plasminogen Activator Activity

scholarly journals Human Prekallikrein (Plasminogen Proactivator): Purification, Characterization and Activation by Activated Factor XII

1977 ◽  
Author(s):  
Bonno N. Bouma ◽  
John H. Griffin
Keyword(s):  
Human Plasma ◽  
Plasminogen Activator ◽  
Clot Lysis ◽  
Factor Xii ◽  
Globulin Fraction ◽  
Factor Xi ◽  
Form Analysis ◽  
Plasminogen Activator Activity ◽  
Fibrin Plate ◽  
Factor Xiia

In order to resolve conflicting reports about the possible identity of prekallikrein and Factor XII-dependent plasminogen proactivator (FXII-PPA), the γ-globulin fractions of prekallikrein-deficient (Fletcher trait) and of normal plasma were assayed for FXII-PPA. Based on both fibrin plate and clot lysis tests, FXII-PPA in the γ-globulin fractions of prekallikrein-deficient plasmas from 2 unrelated patients was undetectable, i.e. <1% of the FXII-PPA in the normal γ-globulin fraction. However, PPA independent of FXII was detected in both the Fletcher and the normal γ-globulin fractions at 4% of the FXII-PPA present in the normal γ-globulin fraction.Human plasma prekallikrein was purified 2,000-fold (specific clotting activity 22 units/mg) and was greater than 95% homogeneous on SDS-gels. FXII-PPA was always copurified with prekallikrein and was totally separated from Factor XI. No Factor XII-dependent or Factor XII-independent plasminogen activator activity was detected in purified Factor XI preparations at 40 units/ml. Purified prekallikrein in its precursor form gave 2 protein bands on SDS-gels at 82,000 and 78,000 MW. Upon reduction, a single 85,000 MW band was observed. Kallikrein and plasminogen activator activity were generated upon incubation with purified human Factor XIIa (28,000 MW form). Analysis of this reaction mixture on SDS-gels without reduction showed 2 bands with apparently identical MW’s as the precursor protein bands, whereas reduction showed cleavage of both protein bands.These results suggest that prekallikrein is identical to FXII-PPA in normal human plasma and that activation of this zymogen by Factor XIIa involves limited proteolytic cleavage.

scholarly journals Polyphosphate colocalizes with factor XII on platelet-bound fibrin and augments its plasminogen activator activity

Blood ◽  
2016 ◽  
Vol 128 (24) ◽  
pp. 2834-2845 ◽  
Author(s):  
Joanne L. Mitchell ◽  
Ausra S. Lionikiene ◽  
Georgi Georgiev ◽  
Anja Klemmer ◽  
Chelsea Brain ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Factor Xii ◽  
Plasminogen Activator Activity ◽  
Key Points

Key PointsPolyP significantly augments the plasminogen activator capacity of FXIIa. Platelet-bound fibrin acts as a reservoir for plasminogen, FXII(a), and polyP.

Deviations in factor XII-dependent plasminogen activator activity in relation to ischaemic heart disease and age

1992 ◽  
Vol 6 ◽  
pp. 27-30 ◽  
Author(s):  
Jørgen Jespersen ◽  
Ole Dyg Pedersen ◽  
Jørgen Gram ◽  
Kristian Korsgaard Thomsen ◽  
Johannes Sidelmann ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischaemic Heart Disease ◽  
Plasminogen Activator ◽  
Factor Xii ◽  
Plasminogen Activator Activity

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

Ontogenesis of Tissue Plasminogen Activator in the Human

1971 ◽  
Vol 25 (03) ◽  
pp. 469-480 ◽  
Author(s):  
B Åstedt ◽  
M Pandolfi
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Vena Cava ◽  
Vasa Vasorum ◽  
Moderate Activity ◽  
Foetal Development ◽  
Plasminogen Activator Activity ◽  
Stage Of Development ◽  
Tissue Plasminogen ◽  
Enzyme Pattern

SummaryThe ontogenesis of tissue plasminogen activator in various tissues was studied in 10 embryos and 58 foetuses with a histochemical method.The first appearance of activator activity was seen in a 4-weeks old embryo. At 8-9 weeks it was seen in the eye, meninges, heart, lungs, kidney and vena cava. In the foetal heart high activity was found in the coronary vessels, which can be regarded as the vasa vasorum of the heart. In the lungs a moderate activity increased at 24 weeks of age, when vascularisation increases more rapidly. Intense activity was seen in the highly vascularized corneoscleral junction of the eye later involved in the drainage of aqueous humor.In the kidney the activity could be related to the vessels, while no activity was seen in the glomeruli, the collecting system or the pelvis. In the vessels the activator activity was fairly high. No activity was seen in any stage of development of the liver.The plasminogen activator activity may be of importance for maintaining the foetomaternal circulation and micro-circulation in rapidly growing foetal organs. In the embryo the enzyme pattern is dominated by protein synthetizing enzymes. During foetal development the enzyme pattern changes owing to supervention of enzymes necessary for the function of the various organs. Plasminogen activator belongs to this latter group. The appearance of plasminogen activator activity may therefore be regarded mainly as a sign of functional maturity of the foetal organs.

Generation Of Factor XII-Dependent Plasminogen Activator Activity In Human Plasma Measured With A Fluorogenic Substrate

1981 ◽  
Author(s):  
G Dooijewaard ◽  
C Kluft
Keyword(s):  
Human Plasma ◽  
Plasminogen Activator ◽  
Minor Role ◽  
Factor Xii ◽  
Dextran Sulphate ◽  
Fluorogenic Substrate ◽  
A Value ◽  
Substrate Activation ◽  
Factor Xiia ◽  
A Minor

A rapid fluorometric assay for measurement of amidolytic activity in human plasma was developed, using the plasminogen activator sensitive synthetic substrate t-BOC-L-valyl--glycyl-L-arginine-β-naphthylamide. The plasma is diluted in a reaction cuvet containing 0.050 M Tris HC1 buffer (pH 8.0) and 150 μM substrate. Activation of plasminogen proactivator(s) is initiated at 37°C by the addition of 10 μg dextran sulphate (MW 500,000)/ml. The concentration of β-naphthyl- amide released is recorded fluorometrically as a function of time. The slope of this curve at any time t is proportional to the concentration of activator. Thus, in a single assay, the entire time-dependent profile of activation and subsequent inhibition is monitored; this provides 1. a value for an optimum plasminogen activator content in the plasma, and 2. the time it takes to reach the optimum. The plot of optimum activator content against μl of plasma added is linear for dilutions more than 100-fold, suggesting that under these conditions the optimum content approaches the content of proactivator(s) originally present.The activator content measured predominantly consists of contributions of a factor XII-dependent process since 1. without dextran sulphate or with plasmas deficient in factor XII or prekallikrein no activity could be generated, and 2. plots of optimum activator content against dextran sulphate concentration show sigmoidal-shaped saturation curves as found previously for the kallikrein generation in human plasma. Contributions of factor XIIa and kallikrein only partly account for the content measured and studies with plasmas deficient in factor XI point to a minor role for this factor, if any. Further identification of the activator (s) involved is in progress.

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