scholarly journals Cleavage of human high molecular weight kininogen by factor XIa in vitro. Effect on structure and function.

1985 ◽  
Vol 260 (19) ◽  
pp. 10856-10863
Author(s):  
C F Scott ◽  
L D Silver ◽  
A D Purdon ◽  
R W Colman
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Structure And Function ◽  
High Molecular Weight Kininogen ◽  
Factor Xia ◽  
And Function ◽  
Vitro Effect

Surface Independent Factor XI Activation by Thrombin in the Presence of High Molecular Weight Kininogen

1994 ◽  
Vol 72 (03) ◽  
pp. 397-402 ◽  
Author(s):  
Peter A Kr von dem Borne ◽  
Stefan J Koppelman ◽  
Bonno N Bouma ◽  
Joost C M Meijers
Keyword(s):  
Molecular Weight ◽  
Blood Coagulation ◽  
High Molecular Weight ◽  
Dextran Sulfate ◽  
Factor Xa ◽  
Factor X ◽  
High Molecular Weight Kininogen ◽  
Factor Xi ◽  
Factor Xia

SummaryA deficiency of one of the proteins of the contact system of blood coagulation does not result in a bleeding disorder. For this reason activation of blood coagulation via this system is believed to be an in vitro artefact. However, patients deficient in factor XI do suffer from variable bleeding abnormalities. Recently, an alternative pathway for factor XI activation has been described. Factor XI was found to be activated by thrombin in the presence of dextran sulfate as a surface. However, high molecular weight kininogen (HK), to which factor XI is bound in plasma, and fibrinogen were shown to block this activation suggesting it to be an in vitro phenomenon. We investigated the thrombin-mediated factor XI activation using an amplified detection system consisting of factors IX, VIII and X, which was shown to be very sensitive for factor XIa activity. This assay is approximately 4 to 5 orders of magnitude more sensitive than the normal factor XIa activity assay using a chromogenic substrate. With this assay we found that factor XI activation by thrombin could take place in the absence of dextran sulfate. The initial activation rate was approximately 0.3 pM/min (using 25 nM factor XI and 10 nM thrombin). The presence of dextran sulfate enhanced this rate about 8500-fold. A very rapid and complete factor X activation was observed in the presence of dextran sulfate. Although only minute amounts of factor XIa were formed in the absence of dextran sulfate, significant activation of factor X was detected in the amplification assay within a few minutes. HK inhibited the activation of factor XI by thrombin strongly in the presence, yet only slightly in the absence of dextran sulfate (26 and 1.2 times, respectively). Despite the strong inhibition of HK on the activation of factor XI by thrombin in the presence of dextran sulfate, HK had only a minor effect on the factor Xa generation.We conclude that activation of factor XI by thrombin can take place regardless of the presence of a surface or HK. This activation might therefore be physiologically relevant. The inhibitory effect of HK on the thrombin-mediated factor XI activation is largely dextran sulfate dependent. Due to the amplification in the intrinsic system, trace amounts of factor XIa might generate physiological sufficient amounts of factor Xa for an adequate haemostatic response.

Pro-angiogenic effect of human kallikrein-related peptidase 12 (KLK12) in lung endothelial cells does not depend on kinin-mediated activation of B2 receptor

2013 ◽  
Vol 394 (3) ◽  
pp. 385-391 ◽  
Author(s):  
Thomas Kryza ◽  
Gilles Lalmanach ◽  
Marion Lavergne ◽  
Fabien Lecaille ◽  
Pascale Reverdiau ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Endothelial Cells ◽  
High Molecular Weight ◽  
High Molecular Weight Kininogen ◽  
Kinin Receptor ◽  
Angiogenic Effect ◽  
Lung Endothelial Cells ◽  
Carboxy Terminal

Abstract Kallikrein-12 (KLK12) may play an important role in angiogenesis modulating proangiogenic factor bioavailability and activating the kinin receptor B2 pathway. We studied whether KLK12 had an impact on angiogenesis and the activation of kinin receptor B2 results from the KLK12-dependent generation of kinins. KLK12 efficiently hydrolyzed high molecular weight kininogen, liberating a fragment containing the carboxy-terminal end of kinins. The kininogenase activity of KLK12 was poor, however, due to the cleavage resistance of the N-terminal side of the kinin sequence. A very low amount of kinins was accordingly released after in vitro incubation of high molecular weight kininogen with KLK12 and thus the proangiogenic activity of KLK12 in lung endothelial cells was not related to a kinin release.

High Molecular Weight Kininogen Is Cleaved by FXIa at Three Sites: Arg409-Arg410, Lys502-Thr503 and Lys325-Lys326

2000 ◽  
Vol 83 (05) ◽  
pp. 709-714 ◽  
Author(s):  
T. Mauron ◽  
B. Lämmle ◽  
W. A. Wuillemin
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Coagulation Factor ◽  
Cleavage Sites ◽  
High Molecular Weight Kininogen ◽  
Surface Binding ◽  
Amino Acid Sequence Analysis ◽  
Sds Page ◽  
System Activation

SummaryWe investigated the cleavage of high molecular weight kininogen (HK) by activated coagulation factor XI (FXIa) in vitro. Incubation of HK with FXIa resulted in the generation of cleavage products which were subjected to SDS-Page and analyzed by silverstaining, ligandblotting and immunoblotting, respectively. Upon incubation with FXIa, bands were generated at 111, 100, 88 kDa on nonreduced and at 76, 62 and 51 kDa on reduced gels. Amino acid sequence analysis of the reaction mixtures revealed three cleavage sites at Arg409-Arg410, at Lys502-Thr503 and at Lys325-Lys326. Analysis of HK-samples incubated with FXIa for 3 min, 10 min and 120 min indicated HK to be cleaved first at Arg409-Arg410, followed by cleavage at Lys502-Thr503 and then at Lys325-Lys326.In conclusion, HK is cleaved by FXIa at three sites. Cleavage of HK by FXIa results in the loss of the surface binding site of HK, which may constitute a mechanism of inactivation of HK and of control of contact system activation.

Cleaved high-molecular-weight kininogen inhibits neointima formation following vascular injury

2015 ◽  
Vol 114 (09) ◽  
pp. 603-613 ◽  
Author(s):  
Jan-Marcus Daniel ◽  
Fabian Reich ◽  
Jochen Dutzmann ◽  
Simona Weisheit ◽  
Rebecca Teske ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Vascular Injury ◽  
Lesion Size ◽  
Local Application ◽  
Neointima Formation ◽  
Cellular Interactions ◽  
High Molecular Weight Kininogen ◽  
Extracellular Matrix Components

SummaryCleaved high-molecular-weight kininogen (HKa) or its peptide domain 5 (D5) alone exert anti-adhesive properties in vitro related to impeding integrin-mediated cellular interactions. However, the anti-adhesive effects of HKa in vivo remain elusive. In this study, we investigated the effects of HKa on leukocyte recruitment and neointima formation following wire-induced injury of the femoral artery in C57BL/6 mice. Local application of HKa significantly reduced the accumulation of monocytes and also reduced neointimal lesion size 14 days after injury. Moreover, C57BL/6 mice transplanted with bone marrow from transgenic mice expressing enhanced green fluorescence protein (eGFP) showed a significantly reduced accumulation of eGFP+-cells at the arterial injury site and decreased neointimal lesion size after local application of HKa or the polypeptide D5 alone. A differentiation of accumulating eGFP+-cells into highly specific smooth muscle cells (SMC) was not detected in any group. In contrast, application of HKa significantly reduced the proliferation of locally derived neointimal cells. In vitro, HKa and D5 potently inhibited the adhesion of SMC to vitronectin, thus impairing their proliferation, migration, and survival rates. In conclusion, application of HKa or D5 decreases the inflammatory response to vascular injury and exerts direct effects on SMC by impeding the binding of integrins to extracellular matrix components. Therefore, HKa and D5 may hold promise as novel therapeutic substances to prevent neointima formation.

scholarly journals BIOSURFACTANTS FROM MARINE MICROORGANISMS: I. STRUCTURE AND FUNCTIONS

2021 ◽  
pp. 6-27
Author(s):  
B. N. Galkin ◽  
M. O. Finogenova ◽  
А. S. Semenets ◽  
M. B. Galkin ◽  
T. O. Filipova
Keyword(s):  
Fatty Acids ◽  
Molecular Weight ◽  
High Molecular Weight ◽  
Structure And Function ◽  
Physiological Characteristics ◽  
Low Molecular Weight ◽  
Marine Microorganisms ◽  
And Function ◽  
Structure And Functions

Marine microorganisms have unique metabolic and physiological characteristics and are an important source of new biomolecules such as biosurfactants. Low molecular weight surfactants are glycolipids, phospholipids, fatty acids, lipopeptides and lipoproteins, and high molecular weight surfactants are mixtures of heteropolysaccharides, lipopolysaccharides, lipoproteins and proteins. The main general of bacteria that synthesize biosurfactants are Pseudomonas, Bacillus, Acinetobacter, Antarctobacter, Rhodococcus, Halomonas, Alcanivorax, Pseudoalteromonas and Marinobacter. This review examines the structure and function of biosurfactants isolated from marine microorganisms.

scholarly journals Fitzgerald factor (high molecular weight kininogen) clotting activity in human plasma in health and disease in various animal plasmas

Blood ◽  
1976 ◽  
Vol 48 (6) ◽  
pp. 941-947 ◽  
Author(s):  
H Saito ◽  
G Goldsmith ◽  
R Waldmann
Keyword(s):  
Molecular Weight ◽  
Human Plasma ◽  
High Molecular Weight ◽  
Lupus Erythematosus ◽  
Mammalian Species ◽  
Clotting Factor ◽  
Factor Activity ◽  
High Molecular Weight Kininogen ◽  
Amphibian Species

Abstract Fitzgerald factor (high molecular weight kininogen) is an agent in normal human plasma that corrects the impaired in vitro surface- mediated plasma reactions of blood coagulation, fibrinolysis, and kinin generation observed in Fitzgerald trait plasma. To assess the possible pathophysiologic role of Fitzgerald factor, its titer was measured by a functional clot-promoting assay. Mean +/- SD in 42 normal adults was 0.99+/-0.25 units/ml, one unit being the activity in 1 ml of normal pooled plasma. No difference in titer was noted between normal men and women, during pregnancy, or after physical exercise. Fitzgerald factor activity was significantly reduced in the plasmas of eight patients with advanced hepatic cirrhosis (0.40+/-0.09 units/ml) and of ten patients with disseminated intravascular coagulation (0.60+/-0.30 units/ml), but was normal in plasmas of patients with other congenital clotting factor deficiencies, nephrotic syndrome, rheumatoid arthritis, systemic lupus erythematosus, or sarcoidosis, or under treatment with warfarin. The plasmas of 21 mammalian species tested appeared to contain Fitzgerald factor activity, but those of two avian, two repitilian, and one amphibian species did not correct the coagulant defect in Fitzgerald trait plasmas.

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