Endothelial cells produce a substance that inhibits contact activation of coagulation by blocking the activation of Hageman factor.

Human umbilical vein endothelial cells (HUVECs) produce a property that impairs the generation of coagulant and amidolytic activity initiated when normal human plasma is exposed to glass. This inhibitory property blocks the adsorption of Hageman factor (factor XII) to glass, thereby preventing the activation of Hageman factor, but does not impair the coagulant or amidolytic activity of already activated Hageman factor (factor XIIa). This property in HUVEC lysates could be neutralized by a purified preparation of Hageman factor but not by purified prekallikrein or high molecular mass kininogen.

Mechanism of enhanced kinin release from high molecular weight kininogen by plasma kallikrein after its exposure to plasmin.

When purified high molecular weight kininogen was incubated with streptokinase-activated plasmin and kallikrein, a larger amount of kinin was released than would have been predicted from the effect of either enzyme alone. To determine the mechanism of this enhancement, high molecular weight kininogen was digested sequentially with these enzymes, and the rates of kinin release and sites of cleavage were determined. Conversion of 133 kd native high molecular weight kininogen to two-chain 112 kd or 102 kd derivatives by plasmin more than doubled the rate of kinin release by kallikrein.

Plasma kininogen concentration: the low level in cord blood plasma and age dependence in adults.

Antigenic concentration of total kininogen, kinin liberated in vitro, and the antigenic concentration of high molecular weight (HMW) kininogen was measured in 58 different samples of cord blood plasma and in plasma samples from 67 healthy blood donors. Total kininogen and kinin concentration in cord blood plasma was more than twice as low as in pooled plasma of adult persons, and the concentration of HMW-kininogen in cord blood plasma was close to one-third of normal. The concentration of total kininogen and of HMW-kininogen increased with age in adults.

[Concentration of kininogens and low molecular kininogen antigen in plasma of pregnant rabbits and newborn progeny in health and following intravenous infusion of purified thrombin].

High levels of trypsin-releasing kinin and low molecular plasma kininogen antigen were detected in plasma of pregnant female rabbits. Respective values in plasma of their new born progeny was 2.7 times lower than that in maternal plasma.

Granulocyte elastase cleaves human high molecular weight kininogen and destroys its clot-promoting activity.

Purified human granulocyte elastase cleaved purified human high molecular weight (HMW) kininogen into multiple low molecular weight fragments, and destroyed the clot-promoting activity of the HMW kininogen. Elastase digestion did not release kinin or destroy the bradykinin portion of the HMW kininogen molecule; kallikrein could release kinin from the elastase-induced low molecular weight digestion products of HMW kininogen. Purified alpha 1-antitrypsin prevented the destruction of the clot-promoting activity of HMW kininogen by elastase; it also delayed the clotting of normal plasma.

Comparison of properties of monoclonal and polyclonal antibodies against the light chain of human high molecular weight kininogen.

A murine hybridoma monoclonal line-secreted antibody (C3G5) against the light chain of human high molecular weight kininogen (HMWK), which consisted of gamma-1 kappa isotype, was largely composed of 190 kd molecules, and gave an optimal reaction when used in an equimolar concentration with HMWK. It did not influence the initial digestion of HMWK or the amount of kinin released by kallikrein. Pretreatment of HMWK with C3G5 antibodies did not augment or inhibit its coagulant properties, nor did pretreatment interfere with its adsorption on kaolin or on the ion-exchange resin diethylaminoethyl (DEAE) Sephadex A-50.

Comparison of human high molecular weight kininogen digestion by plasma kallikrein and by plasmin. A revised method of purification of high molecular weight kininogen.

Both kallikrein and plasmin readily released 112,000 and 102,000 molecular weight derivatives from purified human high molecular weight (HMW)-kininogen. In each instance, these early digestion products were composed of disulfide-linked chains of 64,000 and 58,000 molecular weights. Under the experimental conditions used, kallikrein failed to release additional cleavage fragments from HMW-kininogen when it had been previously digested by plasmin, whereas HMW-kininogen pretreated with kallikrein was then cleaved by plasmin into several derivatives of decreasing molecular size.

Experimental arteriosclerosis and the plasma kininogen and low molecular weight kininogen antigen concentration in rabbits.

A decrease in trypsin-releasable kinin and in low molecular weight kininogen antigen concentrations was observed in plasma of rabbits with cholesterol-induced arteriosclerosis. In rabbits receiving normal diet for 30 days after 30 days of cholesterol almost complete normalization of the morphological status was observed, which was accompanied by normalization of plasma kinin concentration and by higher than normal concentration of kininogen antigen measured. These changes were not observed in animals receiving normal diet for 30 days after 60 days of cholesterol administration.

Some molecular and functional changes in high molecular weight kininogen induced by plasmin and trypsin.

When purified human HMW-kininogen was digested by plasmin, its specific antigenic properties were initially enhanced and then gradually destroyed, but its clot-promoting activity (Fitzgerald factor activity) was only slightly decreased. When endogenous serum plasminogen was activated by streptokinase, similar alterations in specific HMW-kininogen antigens and Fitzgerald factor activity occurred. In contrast, trypsin induced increased antigenic properties initially, but readily destroyed the Fitzgerald factor activity and less readily destroyed the specific HMW-kininogen antigenic properties in purified HMW-kininogen and in normal human serum.

The concentration of high molecular weight kininogen antigen in homogenates of various human tissues.

The concentration of high molecular weight kininogen, measured in human tissue homogenates, was 2-3 times higher in kidneys, adrenals and thyroid than in homogenates of lung, heart, liver and spleen. No measurable quantities of this protein were found in homogenates of brain and skeletal muscles.

Plasma high molecular weight kininogen concentration in health and in chosen impairments of haemostasis. Evidence that plasmin uncovers a new antigenic site in high molecular weight kininogen.

High molecular weight kininogen (HMW-kininogen) concentration was measured in the plasma of healthy blood donors, patients with haemophilia A, idiopathic thrombocytopoenic purpura, deep vein thrombosis treated with oral anticoagulants and patients treated with streptokinase (SK). The concentration of HMW-kininogen in the plasma of healthy subjects was 92 +/- 15 micrograms/ml. The values obtained in patients' plasma were not different statistically.

Prekallikrein deficiency in a kindred with kininogen deficiency and Fitzgerald trait clotting defect. Evidence that high molecular weight kininogen and prekallikrein exist as a complex in normal human plasma.

Plasma from an individual with a hereditary deficiency of kininogens is deficient in kininogen antigens; heterozygous relatives are partially deficient in plasma kininogen antigens. In addition, plasma from the proband is partially deficient in functional and antigenic properties of a plasma prekallikrein, and the relatives heterozygous for kininogen deficiency are also partially deficient in the plasma prekallikrein. It is possible that the defects are both inherited and that the inheritance of a deficiency of prekallikrein is genetically linked to the inheritance of a deficiency of kininogen.

Influence of plasma hemostasis on insulin action in vitro.

The influence of various components of plasma hemostatic system on the assimilation of glucose by isolated rat hemidiaphragm in the presence of insulin was investigated. The addition of streptokinase and human plasminogen to the incubation medium decreased the rate of glucose assimilation. This effect did not occur when trasylol, an inhibitor of plasmin, was added to the assay system.