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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lysis of fibrin clots on the surface of cultured human omental tissue microvascular endothelial cells (HOTMEC) and cultured human umbilical vein endothelial cells (HUVEC) was studied. Fibrin clots were made by mixing fibrinogen, plasminogen and thrombin on the surface of both cell types. Clot lysis was seen only on the surface of HOTMEC, which were found to synthesize about 100-fold more tissue plasminogen activator (tPA) antigen than HUVEC. Clot lysis of HOTMEC could be blocked by anti-tPA IgG but was not affected by the incorporation of exogenous plasminogen activator (PAI) into the clot in concentrations (75 arbitrary units) exceeding the tPA activity (21 +/- 2.5 IU) of the cells. Thus, it is likely that tPA secreted by HOTMEC is protected from inhibition by PAI in the presence of fibrin and endothelial cells. The stimulation of EC to release an excess of tPA over PAI, in contrast to the secretion of an excess of PAI over tPA found in unstimulated cells in the absence of fibrin, is obviously no prerequisite for the initiation of fibrinolysis on the surface of HOTMEC. As thrombin was used for clot formation, its influence on tPA and PAI synthesis of both cell types was investigated. In contrast to HOTMEC, which were not affected by alpha-thrombin, HUVEC revealed a dose-dependent increase in tPA and PAI synthesis upon incubation with the enzyme. This increase in tPA production by HUVEC was not sufficient to lyse the clots within 48 hours. Furthermore, HUVEC behaved differently towards thrombin as these cells in contrast to HOTMEC revealed the typical shape change reaction upon incubation with the enzyme.
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PMID:Clot lysis mediated by cultured human microvascular endothelial cells. 314 47

Three of 13 patients with intracranial meningiomas showed the pre- and postoperative elevation of tissue-type plasminogen activator (t-PA) related fibrinolytic activity in euglobulin fractions (EFA). During operation, two of these three patients showed a significant elevation of the level of fibrin(ogen) degradation products and oozing in the operating field. However, oozing was not observed in the third patient who had been given tranexamic acid preoperatively. Fibrin autography revealed that a broad lytic band of mol wt 50-60 kDa, probably free t-PA, appeared in the plasma obtained from two of the three patients after operation when EFA elevated significantly. In all patients studied, the t-PA antigen levels were normal preoperatively but increased both during and after operation, and correlated mainly with the intensities of a lytic band of mol wt 110 kDa, probably t-PA complexed with its major inhibitor (PAI-1). These results suggest that the excessive fibrinolysis can induce the local hemorrhagic diathesis during operation and may be related to t-PA function in plasma.
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PMID:Tissue-type plasminogen activator in patients with intracranial meningiomas. 314 49

Nonenzymatic glycation of fibrinogen is species independent and depends only on the glucose concentration in the incubation mixture under selected in vitro conditions. An increased fibrin monomer aggregation in the presence of Ca2+ ions and a decreased proteolytic susceptibility of nonenzymatically glycated fibrinogens may favour the development of thrombophilic states. Blocking of lysine residues as well as restricted conformational changes induced by glucose attachment may be responsible for these effects. Fibrin stabilization by factor XIII is not impaired by nonenzymatic glycation of fibrinogen. Attachment of aortic endothelial cells to fibrin films from glycated fibrinogens is diminished. This phenomenon may be the result of blocked plasminogen activator binding sites in fibrin by nonenzymatic glycation. These effects may contribute in vivo to the accumulation of fibrin in those tissues most frequently affected by diabetic complications.
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PMID:Properties of in vitro nonenzymatically glycated plasma fibrinogens. 366 59

Fibrin deposition is prominent in the histopathologic features of chronic interstitial lung disease. Human alveolar macrophages can potentially modulate this process because normal macrophages synthesize and express the initial enzymes of both coagulation and fibrinolytic pathways. In the present study, we examined the cell-associated procoagulant activity of macrophages lavaged from patients with sarcoidosis (n = 14) or idiopathic pulmonary fibrosis (n = 13) and compared the enzyme activities with that of a group of normal volunteers (n = 16). Cells from sarcoid patients had a mean (+/- 1 SD) tissue factor activity of 1,491 +/- 2,160 units/5 X 10(5) cells, as compared with a mean of 480 units (range, 140 to 1,000 units) for normal control subjects. The same cells had a mean plasma Factor VII equivalent of 4.7 ng/10(6) cells, as compared with 0.81 ng/10(6) cells (range, 0.2 to 2.0 ng) for the normal control subjects. The enhanced activity correlated with disease activity as judged by radiographic stage: only patients with Stage II or Stage III disease had consistently elevated procoagulant activity. There was no correlation of procoagulant activity with the percentage of lymphocytes in the alveolar fluid. Cells from patients with idiopathic pulmonary fibrosis also had increased tissue factor (mean, 2,980 +/- 2,619 units) but less consistently elevated Factor VII. There was considerable variation in both procoagulant activity and cell differentials between lavage sites in 10 patients in whom 2 separate lobes were studied concurrently. In addition, we examined the plasminogen activator (PA) activities of lavaged cells and concentrated alveolar fluids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormalities in pathways of alveolar fibrin turnover among patients with interstitial lung disease. 395 52

Considering the proved interaction of fibrin with fibroblasts and the seemingly decisive role of structural and functional changes ("modulation") of these cells in the evolution of Dupuytren's contracture, research has been carried out in order to investigate the fibrinolytic capacity and the possible presence of fibrin/fibrinogen in the palmar fascia of subjects operated upon for Dupuytren's Disease. Fibrin/fibrinogen were detected by a direct immunofluorescence technique and fibrinolytic activity was assessed by a fibrin plate method. A remarkable decrease of fibrinolytic activity and the presence of fibrin/fibrinogen were observed in small nodules in the early stage of disease, whereas large nodules showed a high amount of plasminogen activator enzymes. Small nodules seem to form and increase by progressive adhesion of fibroblasts to the polymerizing fibrin, while high fibrinolytic activity of large nodules probably results from "modulation" of many fibroblasts into contractile myofibroblasts and could therefore be considered as a biochemical sign of the evolutionary phase of Dupuytren's contracture.
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PMID:Fibrin/fibrinogen and fibrinolytic activity of the palmar fascia in Dupuytren's contracture. 395 50

To clarify the clinical importance of tissue-plasminogen activator (t-PA) on the thrombosis, it is essential to be measured t-PA level in human plasma. Taking advantage of strong affinity of t-PA to fibrin, t-PA was isolated with Fibrin/Celite column chromatography. Immunological activities of t-PA of plasma samples determined by ELISA and the elution pattern of it on Fibrin/Celite column chromatography were studied. The results are as follows: The t-PA in human plasma was consisted of fibrin adsorbable t-PA and fibrin nonadsorbable t-PA. Both types of t-PA could be measured separately by using of Fibrin/Celite column chromatography. The fibrin adsorbable t-PA fraction showed two types of molecular size (major peak was Mr congruent to 70,000, minor peak was Mr congruent to 100,000) on Sephadex G-200 chromatography. The level of t-PA in plasma samples taken from 20 healthy subjects at rest was 2.4 +/- 1. 9 ng/ml, and concentration of t-PA increased to 10.4 +/- 3.2 ng/ml after venous stasis. But the t-PA level of plasma samples from patients with cerebral thrombosis did not increase after venous stasis. The changes of immunologically determined t-PA in plasma samples induced by venous stasis were not reflected in the fibrinolytic activities of the euglobulin fractions, but well reflected in the fibrinolytic activities of the elution fractions on Fibrin/Celite column chromatography. The level of fibrin nonadsorbable t-PA did not change by venous stasis, but the level of fibrin adsorbable t-PA increased from 5.1 +/- 1.9 ng/ml to 9.7 +/- 2.7 ng/ml in the case of 6 healthy subjects. It is concluded that, the plasma t-PA increased by venous stasis was the fibrin adsorbable t-PA, and it may play a very important role in physiological fibrinolysis.
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PMID:[Analysis of plasminogen activator in human plasma using the method of fibrin/celite column chromatography--with special reference to the determination of fibrin adsorbable tissue-plasminogen activator by ELISA]. 408 66

Twenty-two patients with acute hepatic failure were studied to determine the incidence and magnitude of intravascular coagulation and fibrinolysis and their relation to the severity of bleeding and prognosis. The mean platelet count, Thrombotest, plasminogen activator, and plasminogen were reduced; the reduction in fibrinogen was not statistically significant. Fibrin/fibrinogen degradation products were only moderately increased. Hepatic fibrin deposition was not extensive, being present in 11 of 22 hepatic sections, more in areas of confluent necrosis than in the sinusoids. The combination of increased fibrin/fibrinogen degradation products with decreased plasminogen activator, plasminogen, and thrombocytopenia is consistent with a diagnosis of intravascular coagulation and secondary local fibrinolysis. However, neither of these processes was severe. Severity of bleeding was related only to plasminogen levels and prognosis only to Thrombotest levels. There was no relation between hepatic histological and haematological findings. Heparin therapy is not indicated in the routine management of acute hepatic failure, as intravascular coagulation is not severe and heparin may itself cause massive bleeding.
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PMID:Significance of intravascular coagulation and fibrinolysis in acute hepatic failure. 482 Jun 41

The activation rate of plasminogen by tissue-type plasminogen activator can be increased by fibrin(ogen) fragments. There is a remarkable difference in the effect of these fragments on the stimulation of 1-glu-plasminogen activation and 442-val-plasminogen (mini-plasminogen) activation. Fibrin monomer as well as plasmic fragments Y, D EGTA and D-dimer have a stimulating effect on both 1-glu-plasminogen and 442-val-plasminogen activation, whereas cyanogen bromide fragment FCB2 stimulates only the activation of 1-glu-plasminogen. Results indicate that two types of sites may be operational in fibrin and fibrin(ogen) fragments Y, D EGTA and D-dimer. One type of site (FCB2-related) interacts probably with plasminogen and may be dependent on the kringle 1-4 region; the other type of site probably interacts either with plasminogen in a non-kringle 1-4 region-dependent manner or with tissue-type plasminogen activator.
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PMID:Differences in effects of fibrin(ogen) fragments on the activation of 1-glu-plasminogen and 442-val-plasminogen by tissue-type plasminogen activator. 622 56

Fibrin deposition is prominent in the histopathology of a number of inflammatory lung diseases. Plasmin, activated locally in the lung, can degrade not only this fibrin but potentially structural proteins important to normal lung architecture. Because alveolar macrophages are prominent in inflammatory processes of the lung, we examined the plasminogen activator (PA) activity of human alveolar macrophages. Intact alveolar macrophages from each of 10 healthy subjects expressed PA activity. There was no difference in activity between smoking and nonsmoking individuals. The activator activity was largely cell-associated, but under certain culture conditions, macrophages released a soluble activator into the culture medium. The membrane-bound activator had an apparent molecular mass of 52-55 kD in nonreduced sodium dodecyl sulfate (SDS) gels, and monospecific antibody to urokinase neutralized the enzyme activity. Immunoprecipitation of [35S]methionine-labeled cells showed that human alveolar macrophages actually synthesize the PA in vitro. SDS-gel analysis of the immunoprecipitated material revealed the predominant species of PA to be structurally similar to reduced, active urokinase. We also examined the role of PA in the degradation of both insoluble fibrin and elastin matrices by live macrophages. Cells degraded an insoluble fibrin matrix in the presence of plasminogen whether or not the macrophages contacted the fibrin as long as proteinase inhibitors were not in the culture medium. In the presence of serum proteinase inhibitors, macrophages still degraded a fibrin matrix, but only if they were in contact with the fibrin. Live macrophages also degraded insoluble elastin only when in contact with the elastin but could do so even in the presence of serum proteinase inhibitors. In matrices containing a mixture of fibrin and elastin, cells did not degrade elastin unless plasminogen was added to the medium. These results indicate that normal alveolar macrophages synthesize and express, probably at the cell surface, a PA. The PA is physically and immunochemically similar to urokinase but is membrane bound. The PA is critical to the degradation of fibrin matrices by normal alveolar macrophages. Under tissue conditions where elastin is embedded within other structural proteins, the activator may be rate-limiting in elastin degradation as well. The findings also suggest that live macrophage proteolytic activity is relatively insensitive to the presence of serum proteinase inhibitors, suggesting a mechanism for proteolytic lung injury even in the presence of proteinase-proteinase inhibitor balance in the soluble phase.
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PMID:Degradation of fibrin and elastin by intact human alveolar macrophages in vitro. Characterization of a plasminogen activator and its role in matrix degradation. 636 89

We measured products of thrombin and plasmin action and of the platelet release reaction during exercise to determine if the well-known effect of exercise on in vitro coagulation and fibrinolytic tests reflects activity of these systems in vivo. Plasma fibrinopeptide A, produced by thrombin-mediated proteolysis of fibrinogen, increased with graded treadmill and cycle exercise to postexercise levels of 20--30 times resting values. Fibrin/fibrinogen-related D antigen increased in a similar fashion with peak levels at maximal O2 uptake. Plasma-activated partial thromboplastin times fell as fibrinopeptide A levels increased. Unheated fibrin plate lysis areas increased as D antigen concentrations rose, indicating increased release of plasminogen activator. In contrast to activation of the soluble coagulation and fibrinolytic systems, platelet counts and plasma levels of beta-thromboglobulin, a platelet release protein, did not change significantly with exercise. The effect of exercise on thrombin and plasmin was not influenced by prior physical training, but appeared to be less with cycle exercise than with treadmill exercise.
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PMID:Enhanced thrombin and plasmin activity with exercise in man. 645 Jan 95


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