Localization of distinct functional domains on prekallikrein for interaction with both high molecular weight kininogen and activated factor XII in a 28-kDa fragment (amino acids 141-371)

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.

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Interaction of high molecular weight kininogen binding proteins on endothelial cells

Thrombosis and Haemostasis ◽

10.1160/th03-07-0471 ◽

2004 ◽

Vol 91 (01) ◽

pp. 61-70 ◽

Cited By ~ 34

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.

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Identification of the zinc-dependent endothelial cell binding protein for high molecular weight kininogen and factor XII: identity with the receptor that binds to the globular "heads" of C1q (gC1q-R).

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.93.16.8552 ◽

1996 ◽

Vol 93 (16) ◽

pp. 8552-8557 ◽

Cited By ~ 153

Author(s):

K. Joseph ◽

B. Ghebrehiwet ◽

E. I. Peerschke ◽

K. B. Reid ◽

A. P. Kaplan

Keyword(s):

Molecular Weight ◽

Endothelial Cell ◽

High Molecular Weight ◽

Binding Protein ◽

Factor Xii ◽

High Molecular Weight Kininogen ◽

Cell Binding

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

Blood ◽

10.1182/blood.v55.1.156.156 ◽

1980 ◽

Vol 55 (1) ◽

pp. 156-159 ◽

Cited By ~ 493

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.

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

The International Journal of Artificial Organs ◽

10.1177/039139880002300309 ◽

2000 ◽

Vol 23 (3) ◽

pp. 199-206 ◽

Cited By ~ 27

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.

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