scholarly journals High molecular weight kininogen inhibits fibrinogen binding to cytoadhesins of neutrophils and platelets.

1989 ◽  
Vol 109 (1) ◽  
pp. 377-387 ◽  
Author(s):  
E J Gustafson ◽  
H Lukasiewicz ◽  
Y T Wachtfogel ◽  
K J Norton ◽  
A H Schmaier ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Degradation Products ◽  
Platelet Glycoprotein ◽  
Human Neutrophils ◽  
Human Neutrophil Elastase ◽  
Factor Xii ◽  
High Molecular Weight Kininogen ◽  
Gamma Chain ◽  
Fibrinogen Binding

Fibrinogen inhibited 125I-high molecular weight kininogen (HMWK) binding and displaced bound 125I-HMWK from neutrophils. Studies were performed to determine whether fibrinogen could bind to human neutrophils and to describe the HMWK-fibrinogen interaction on cellular surfaces. At 4 degrees C, the binding of 125I-fibrinogen to neutrophils reached a plateau by 30 min and did not decrease. At 23 and 37 degrees C, the amount of 125I-fibrinogen bound peaked by 4 min and then decreased over time because of proteolysis of fibrinogen by human neutrophil elastase (HNE). Zn++ (50 microM) was required for binding of 125I-fibrinogen to neutrophils at 4 degrees C and the addition of Ca++ (2 mM) increased the binding twofold. Excess unlabeled fibrinogen or HMWK completely inhibited binding of 125I-fibrinogen. Fibronectin degradation products (FNDP) partially inhibited binding, but prekallikrein and factor XII did not. The binding of 125I-fibrinogen at 4 degrees C was reversible with a 50-fold molar excess of fibrinogen or HMWK. Binding of 125I-fibrinogen, at a concentration range of 5-200 micrograms/ml of added radioligand, was saturable with an apparent Kd of 0.17 microM and 140,000 sites/cell. The binding of 125I-fibrinogen to neutrophils was not inhibited by the peptide RGDS derived from the alpha chain of fibrinogen or by the mAb 10E5 to the platelet glycoprotein IIb/IIIa heterodimer. Fibrinogen binding was inhibited by a gamma-chain peptide CYGHHLGGAKQAGDV and by mAb OKM1 but was not inhibited by OKM10, an mAb to a different domain of the adhesion glycoprotein Mac-1 (complement receptor type 3 [CR3]). HMWK binding to neutrophils was not inhibited by OKM1. These observations were consistent with a further finding that fibrinogen is a noncompetitive inhibitor of 125I-HMWK binding to neutrophils. Fibrinogen binding to ADP-stimulated platelets was increased twofold by Zn++ (50 microM) and was inhibited by HMWK. These studies indicate that fibrinogen specifically binds to the C3R receptor on the neutrophil surface through the carboxy terminal of the gamma-chain and that HMWK interferes with the binding of fibrinogen to integrins on both neutrophils and activated platelets.

The Contact Phase of Blood Coagulation in Diabetes Mellitus and in Patients with Vasculopathy

1984 ◽  
Vol 52 (03) ◽  
pp. 221-223 ◽  
Author(s):  
M Christe ◽  
P Gattlen ◽  
J Fritschi ◽  
B Lämmle ◽  
W Berger ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Weight ◽  
Blood Coagulation ◽  
High Molecular Weight ◽  
Negative Correlation ◽  
Factor Xii ◽  
C1 Inhibitor ◽  
High Molecular Weight Kininogen ◽  
Contact Phase ◽  
Α2 Macroglobulin

SummaryThe contact phase has been studied in diabetics and patients with macroangiopathy. Factor XII and high molecular weight kininogen (HMWK) are normal. C1-inhibitor and also α2-macroglobulin are significantly elevated in diabetics with complications, for α1-macroglobulin especially in patients with nephropathy, 137.5% ± 36.0 (p <0.001). C1-inhibitor is also increased in vasculopathy without diabetes 113.2 ± 22.1 (p <0.01).Prekallikrein (PK) is increased in all patients’ groups (Table 2) as compared to normals. PK is particularly high (134% ± 32) in 5 diabetics without macroangiopathy but with sensomotor neuropathy. This difference is remarkable because of the older age of diabetics and the negative correlation of PK with age in normals.

Interaction of high molecular weight kininogen binding proteins on endothelial cells

2004 ◽  
Vol 91 (01) ◽  
pp. 61-70 ◽  
Author(s):  
Baby Tholanikunnel ◽  
Berhane Ghebrehiwet ◽  
Allen Kaplan ◽  
Kusumam Joseph
Keyword(s):  
Molecular Weight ◽  
Endothelial Cell ◽  
High Molecular Weight ◽  
Gel Filtration ◽  
Surface Proteins ◽  
Factor Xii ◽  
High Molecular Weight Kininogen ◽  
Dot Blot ◽  
Cell Plasma ◽  
Molecular Weight Peak

SummaryCell surface proteins reported to participate in the binding and activation of the plasma kinin-forming cascade includes gC1qR, cytokeratin 1 and u-PAR. Each of these proteins binds high molecular weight kininogen (HK) as well as Factor XII. The studies on the interaction of these proteins, using dot-blot analysis, revealed that cytokeratin 1 binds to both gC1qR and u-PAR while gC1qR and u-PAR do not bind to each other. The binding properties of these proteins were further analyzed by gel filtration. When biotinylated cytokeratin 1 was incubated with either gC1qR or u-PAR and gel filtered, a new, higher molecular weight peak containing biotin was observed indicating complex formation. The protein shift was also similar to the biotin shift. Further, immunoprecipitation of solubilized endothelial cell plasma membrane proteins with anti-gC1qR recovered both gC1qR and cytokeratin 1, but not u-PAR. Immunoprecipitation with anti-u-PAR recovered only u-PAR and cytokeratin 1. By competitive ELISA, gC1qR inhibits u-PAR from binding to cytokeratin 1; u-PAR inhibits gC1qR binding to a lesser extent and requires a 10-fold molar excess. Our data suggest that formation of HK (and Factor XII) binding sites along endothelial cell membranes consists of bimolecular complexes of gC1qR-cytokeratin 1 and u-PAR-cytokeratin 1, with gC1qR binding being favored.

scholarly journals Interaction of high molecular weight kininogen, factor XII, and fibrinogen in plasma at interfaces

Blood ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 156-159 ◽  
Author(s):  
L Vroman ◽  
AL Adams ◽  
GC Fischer ◽  
PC Munoz
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Marked Change ◽  
Human Platelets ◽  
Blue Staining ◽  
Factor Xii ◽  
High Molecular Weight Kininogen ◽  
Contact Activation ◽  
Coomassie Blue Staining ◽  
Coated Surfaces

Abstract Using ellipsometry, anodized tantalum interference color, and Coomassie blue staining in conjunction with immunologic identification of proteins adsorbed at interfaces, we have previously found that fibrinogen is the main constituent deposited by plasma onto many man- made surfaces. However, the fibrinogen deposited from normal plasma onto glass and similar wettable materials is rapidly modified during contact activation until it can no longer be identified antigenically. In earlier publications, we have called this modification of the fibrinogen layer “conversion,” to indicate a process of unknown nature. Conversion of adsorbed fibrinogen by the plasma was not accompanied by marked change in film thickness, so that we presumed that this fibrinogen was not covered but replaced by other protein. Conversion is now showen to be markedly delayed in plasma lacking high molecular weight kininogen, slightly delayed in plasma lacking factor XII, and normal in plasma that lack factor XI or prekallikrein. We conclude that intact plasma will quickly replace the fibrinogen it has deposited on glass-like surfaces by high molecular weight kininogen and, to a smaller extent, by factor XII. Platelets adhere preferentially to fibrinogen-coated surfaces; human platelets adhere to hydrophobic nonactivating surfaces, since on these, adsorbed firbinogen is not exchanged by the plasma. The adsorbed fibrinogen will be replaced on glass-like surfaces during surface activation of clotting, and platelets failing to find fibrinogen will not adhere.

FIBRINOGEN BINDS TO HUMAN NEUTROPHILS AT A SITE DISTINCT FROM GPIIb/IIIa

1987 ◽  
Author(s):  
E J Gustafson ◽  
H Lukasiewicz ◽  
A H Schmaier ◽  
S Niewiarowski ◽  
R W Colman
Keyword(s):  
Molecular Weight ◽  
Potential Role ◽  
Human Neutrophils ◽  
Factor Xii ◽  
High Molecular Weight Kininogen ◽  
Large Numbers ◽  
Platelet Membrane Receptor ◽  
Platelet Aggregates ◽  
Attachment Proteins ◽  
A Site

Many observations suggest a potential role for neutrophils in the modulation of hemostasis and thrombosis. Arterial thrombi are characterized by the presence of large numbers of neutrophils lining the perimeter of platelet aggregates. While investigating binding of high molecular weight kininogen (HMWK) to neutrophils, we found that fibrinogen (Fb) could inhibit binding of 125I-HMWK as well as displace HMWK already bound to neutrophils. We therefore initiated studies to determine whether Fb could bind to human neutrophils. Both Zn++ and Ca++ were required for maximal binding of 125I-Fb to neutrophils. Binding did not occur with Ca++ (ZmM) alone and was only 1/3 the maximal amount with Zn++ (50 μM) alone. At 4° the amount of 125I-Fb bound to neutrophils reached a plateau by 15 minutes and remained at this level over the next 30 minutes. At 23° and 37° the amount of 125I-Fb bound peaked by 4 minutes and then decreased over the next 30 minutes indicating receptor-mediated internalization. Excess Fb inhibited binding of 125I-Fb to neutrophils while prekal1ikrein, factor XII, and fibronectin did not. Binding of 125I-Fb was 99% reversible at 4° within 10 minutes with a 50-fold molar excess of Fb and 90% displaceable by excess HMWK. The apparent Kd was approximately 0.45 μM. Arg-Gly-Asp-Ser (RGDS) is a tetrapeptide common to Fb, fibronectin, vitronectin and other cel 1-attachment proteins. Fb has been demonstrated to bind to the glycoprotein IIb/111 a (GPIIb/IIIa) complex which is the platelet membrane receptor for RGDS. Although this RGDS-GPIIb/IIIa interaction occurs with Fb binding to platelets, it is apparently not involved with Fb binding to monocytes. To investigate if Fb binding to neutrophils involved this interaction of GPIIb/II la -RGDS we performed further studies. Binding of 125I-Fb to neutrophils was not inhibited by RGDS nor was it inhibited by a monoclonal antibody (10E5) to the platelet GPI I b/IIIa complex. In addition, the amount of 125I-Fb that hound to neutrophils from a patient with Glanzman's thrombosthenia was the same as that bound to normal neutrophils. These studies indicate that human neutrophils specifically bind Fb at a site similar to HMWK and distinct from GPIIb/IIIa.

Intraindividual Comparison of the Impact of two Selective Apheresis Methods (DALI and HELP) on the Coagulation System

2000 ◽  
Vol 23 (3) ◽  
pp. 199-206 ◽  
Author(s):  
U. Julius ◽  
G. Siegert ◽  
S. Gromeier
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Protein S ◽  
Binding Activity ◽  
Coagulation System ◽  
Factor Xii ◽  
High Molecular Weight Kininogen ◽  
Prothrombin Fragment ◽  
Intraindividual Comparison ◽  
The Impact

We performed an intraindividual comparison of the effect on the coagulation system of two selective apheresis procedures: Direct Adsorption of Lipoproteins (DALI) and Heparin-induced Lipoprotein Fibrinogen Precipitation (HELP). Six patients suffering from heterozygous familial hypercholesterolemia have been treated with 2 sessions of each procedure. Anticoagulation was carried out according to usual recommendations. Blood samples were taken before, immediately after and on the second day after the sessions. We assessed global coagulation tests (prothrombin time, activated partial thromboplastin time), fibrinogen, prothrombin fragment F 1 + 2 and a variety of factors (Factors II, V, VII, XIII, IX, X, XI, XII, XIIa; von Willebrand Factor; collagen-binding activity, prekallikrein, high-molecular weight kininogen) and antagonists (antithrombin III, protein S activity, free protein S). In fact, all parameters measured have been influenced by the apheresis treatment. Fibrinogen is lowered more by HELP, which also has a more definite impact on factors belonging to the prothrombin complex (II, VII, X). In contrast, the major effects of the DALI system have been seen on the intrinsic pathway of the coagulation system (IX, XI, prekallikrein, high-molecular-weight kininogen). With both systems, no increases in activated Factor XII or in prothrombin fragment F1 + 2 have been observed. These data provide a solid basis for individual adaptations of anticoagulant doses.

Sign in / Sign up

Export Citation Format

Share Document