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Biomedical subjects

J Kleniewski

Publications and source records attributed to J Kleniewski.

At least 19 recordsLinked to original sources
PubMed1993

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. A partially purified inhibitory fraction from cell lysates exhibited a single homogeneous band in SDS/PAGE of approximately 22.5 kDa. Inhibitory activity was also found in concentrates of conditioned media from HUVECs, which also impaired the binding of Hageman factor to a surface; it may not be identical with that found in cell lysates.

Cells, Cultured↗
PubMed1992

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. Conversely, digestion of high molecular weight kininogen by kallikrein and then plasmin did not enhance the rate of kinin release. The kallikrein cleavage points that provided 112 kd and 102 kd two-chain high molecular weight kininogen were after residues 437 (Arg-Lys) and 389 (Arg-Ser), whereas those for plasmin were after 438 (Lys-His) and 389 (Arg-Ser). epsilon-Aminocaproic acid, which competes for lysine residues that are critical to the binding of plasminogen or plasmin to substrates, inhibited the digestion of high molecular weight kininogen by plasmin, which is consistent with the evidence that the 438-439 Lys-His was a primary site of plasmin attack on high molecular weight kininogen. Furthermore, this cleavage was observed when plasminogen activation was induced in normal and in prekallikrein or Hageman factor-deficient plasmas. We suggest that the generation of fibrinolytic activity in blood could result in enhanced kinin release by kallikrein in regions of inflammation as a result of the collaborative actions of plasmin and kallikrein on high molecular weight kininogen.

Amino Acids↗
PubMed1991

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. All these findings were highly statistically significant.

Adult↗
PubMed1989

[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. Intravenous infusion of the highly purified bovine thrombin administered to pregnant female rabbits markedly decreased plasma fibrinogen platelet count and increased fibrinogen/fibrin degradation products in blood serum. A marked decrease of trypsin-releasing kinin plasma levels accompanied these changes. No changes in the kininogen antigen levels were seen during the same experiments. Thrombin infusions administered to pregnant female rabbits did not produce measurable changes in trypsin-releasing kinin levels and plasma low molecular kininogen antigen in the progeny obtained for the investigations with the aid of cesarean section.

Animals↗
PubMed1988

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. Elastase may play a significant role in altered hemostasis as well as fibrinolysis, in areas of inflammation to which polymorphonuclear leukocytes have been attracted.

Blood Coagulation↗
PubMed1988

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. The epitope that reacted with this antibody was localized to a portion of the light chain within 6 kd of the carboxy-terminus of the molecule near the single cysteine of this chain, at residue 614. This monoclonal antibody reacted with an epitope that was stable during early plasmin digestion. The amounts of antigens reactive with a polyclonal antibody to the light chain were increased during the same period of plasmin digestion. Prolonged plasmin digestion reduced the amounts of both types of light chain antigens. During kallikrein digestion, the amount of epitope reactive with C3G5 antibody was unaffected, whereas the concentration of antigens detected with polyclonal anti-light chain antibodies was increased throughout digestion. Therefore, light chain antigens reactive with the polyclonal antibody are probably in the interior of the uncleaved molecule and become exposed after initial cleavage, which probably facilitates changes in the conformation of the molecule. The epitope reactive with monoclonal antibodies is probably on the surface of the uncleaved molecule.

Animals↗
PubMed1987

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. The profound molecular changes induced by plasmin were only accompanied by partial kinin release. Plasmin cleavage dissociated procoagulant activity from at least one antigenic site of HMW-kininogen light chain. Moreover, kinin activity could be released from a cleavage product of HMW-kininogen containing light but not heavy chain antigens, indicating that plasmin had cleaved this kininogen on the N-terminal side of the bradykinin region of the molecule. Cleavage of HMW-kininogen by kallikrein readily released bradykinin, whereas kinin release by plasmin was slower and the cleavage pattern different. It is, therefore, unlikely that plasmin is a major source of bradykinin release in plasma. A method of isolating HMW-kininogen from human plasma is described that provides a homogeneous single band of kininogen, with a recovery of approximately 44% with respect to that in plasma in a period of 5 days.

Chromatography↗
PubMed1985

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. No data were obtained suggesting a massive kinin release during induction of arteriosclerosis by experimental hypercholesteremia. The possibility of intense kinin formation during a period of repair of the morphological changes was discussed.

Animals↗
PubMed1982

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. When normal serum was treated with streptokinase, the antigenic properties shared by HMW and LMW-kininogens were in Sephadex G-200 fractions of lower molecular weight than in the case of untreated serum, but the elution volumes of specific HMW-kininogen antigens and Fitzgerald factor activity were not significantly altered. When prekallikrein-deficient serum was subjected to the same G-200 gel filtration process, there was a broad overlap in the elution volumes of antigens shared by both HMW and LMW-kininogens with specific HMW-kininogen antigenic and coagulant properties, which remained after streptokinase treatment of the serum. Depsite the disparate rates of destruction of the antigenic and clot-promoting portion of HMW-kininogen by proteases these properties did not separate from one another during ion exchange chromatography.

Blood Coagulation Factors↗
PubMed1979

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. In the plasma of patients treated with repeated infusion of SK, a significant increase of HMW-kininogen antigen activity was noted after each injection of the drug. Similar results were obtained when SK was added to plasma "in vitro" or when a purified preparation of HMW-kininogen was treated with plasmin. These and additional data obtained suggest that plasmin uncovers in the HMW-kininogen molecule a new antigenic site(s) common to HMW-kininogen and low molecular weight kininogen and new antigenic site(s) specific only for HMW-kininogen.

Absorption↗
PubMed1977

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. Alternatively, it is possible that the deficiency of prekallikrein may be due to its hypercatabolism which could be a consequence of a deficiency of high molecular weight kininogen that may stabilize the prekallikrein in plasma. Evidence to support this possibility is presented by the fact that prekallikrein and high molecular weight kininogen apparently exist as a complex in normal plasma, because monospecific antiserum to kininogen removed both high molecular weight kininogen and prekallikrein from plasma, and vice versa. Moreover, prekallikrein was not adsorbed from kininogen-deficient plasma by antiserum to kininogen unless high molecular weight kininogen was first added to the plasma. Low molecular weight kininogen did not participate in these reactions.

Blood Coagulation↗
PubMed1975

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. The glucose assimilation by hemidiaphragms incubated in buffer with glucose and insulin was not influenced by thrombin, fibrinopeptides, fibrin degradation products, plasminogen, streptokinase or trasylol added separately to the assay system. The mechanism of the influence of plasmin on insulin action was partly elucidated in further experiments. Thus, less 125I-insulin was bound by isolated fat cells preincubated with plasmin than by control cells.

Animals↗