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

Plasma levels of antithrombin III, alpha 2-macroglobulin and inter-alpha-trypsin inhibitor, as well as those of various clotting, complement and other plasma factors, were significantly decreased in 18 patients suffering from hyperdynamic septic shock. A similar statistically significant reduction of the concentrations of several plasma factors (prothrombin and antithrombin III, plasminogen and alpha 2-plasmin inhibitor, complement factor C3 and clotting factor XIII) was observed in experimental endotoxaemia. In this model the reduction in the plasma levels of these factors was considerably diminished by the intravenous injection of a granulocytic elastase--cathepsin G inhibitor of lower molecular weight from soybeans. The results of both studies indicate that consumption of plasma factors in the course of Gram-negative sepsis proceeds not only via the classical routes (by activation of the clotting, fibrinolytic and complement cascades by system-specific proteinases such as thrombokinase or the plasminogen activator) but also to an appreciable degree of unspecific degradation of plasma factors by neutral proteinases such as elastase and cathepsin G. The endotoxin-induced release of both sorts of proteinases, the system-specific ones and the unspecific lysosomal proteinases from leucocytes and other cells, is likely to be mainly responsible for the consumption of antithrombin III and alpha-2-macroglobulin via complex formation (followed by elimination of the complexes) and the increased turnover of the inter-alpha-trypsin inhibitor as observed in the clinical study. The therapeutic use of an exogenous elastase--cathepsin G inhibitor in the experimental model was stimulated by the observation that human mucous secretions contain and acid-stable inhibitor of the neutral granulocytic proteinases, called HUSI-I or antileucoproteinase. This inhibitor protects mucous membranes and soluble proteins against proteolytic attack by leucocytic proteinases released in the course of a local inflammatory response. Preliminary results indicate that HUSI-I, which is produced by the epithelial cells of mucous membranes, does not belong to any known structural type of acid-stable proteinase inhibitor. The search for other candidates suitable for medication in humans led to the discovery of a potent elastase--cathepsin G inhibitor, called eglin, in the leech Hirudo medicinalis. This acid-stable inhibitor with a molecular weight close to 8100 has an unusual structural property in that the structure of the molecule is not stabilized by any disulphide bridge.
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PMID:Proteinase inhibitors in severe inflammatory processes (septic shock and experimental endotoxaemia): biochemical, pathophysiological and therapeutic aspects. 39 95

The effect of surface-bound immune complexes on the secretion of neutral proteases by human peripheral monocytes was examined. Monocytes cultured on 125I-fibrin secreted plasminogen activator in a continuous fashion. Monocytes incubated on 125I-fibrin with surface-bound immune complexes displayed a burst of plasminogen-independent fibrinolytic activity, whereas no release of plasminogen activator was observed through 21 h. The plasminogen-independent fibrinolytic enzymes were derived from monocytes and not from lymphocytes or contaminating polymorphonuclear neutrophils. The effects of various protease inhibitors on the secretion of plasminogen-dependent and independent enzymes were determined. Chymostatin selectively inhibited the monocyte-derived plasminogen activators. Similar effects of chymostatin were observed on human urokinase in the absence of cells. The predominant protease producing plasminogen-independent fibrinolysis exhibited responses to inhibitors characteristic of leukocyte elastase. When monocytes were cultured on 125I-fibrin with adherent immune complexes approximately equal to 40% of the solubilized radioactivity represented deiodination and not proteolysis. It was concluded that culture of human monocytes on surface-bound immune complexes stimulates the secretion of plasminogen-independent fibrinolytic proteases, primarily elastase, and of deiodinating enzymes. Under these conditions, plasminogen activator secretion is inhibited. Neutral proteases secreted from newly recruited monocytes may contribute to tissue injury in human diseases characterized by the presence of adherent immune complexes.
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PMID:Neutral protease secretion by human monocytes. Effect of surface-bound immune complexes. 42 65

Normal human plasma contains acid-stable as well as labile plasminogen activators. The activity of activators in plasma euglobulins was inhibited by EACA in an uniform pattern, similar to that obtained with the major activators in human uterine tissue or with the purified porcine tissue activator, but different from the patterns obtained with plasmin or with urokinase. Gel filtration at high ionic strength separated activators corresponding to particle sizes of 60,000 dalton and about 10,000 dalton, corresponding to two activators similarly obtained from human tissue. The 60,000 dalton activator was precipitated in the euglobulin fraction. Its concentration increased in plasma after exercise. The 10,000 dalton activator was found mainly in the supernatant. Gel filtration in 0.15 M solutions yielded activators in fractions of molecular sizes of 100-140,000 dalton and 200,000 dalton or larger. The activity of normal and exercise euglobulins was inhibited by antiserum to a plasminogen activator prepared from porcine tissue, but it was not inhibited by antiserum to urokinase. Plasminogen activators in human plasma euglobulins resembled immunochemically the activators in human uterine tissue.
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PMID:Separation of plasminogen activators from human plasma and a comparison with activators from human uterine tissue and urine. 48 46

Fibrinolytic studies in euglobulin fractions of Fletcher trait plasma (deficient in prekallikrein) revealed reduced activities as compared to normal plasma. A quantitative assay for total plasminogen activator plus proactivator in plasma showed that the amount in Fletcher trait patients is about half of normal (normal = +/- 100 blood activator units [BAU]/ml). Plasma kallikrein partially purified in a high and low molecular weight form exerted plasminogen activator activity amounting to 10-15 BAU/ml plasma. So, the absence of kallikrein in the deficient plasma cannot fully account for the reduction in activator activity. Additions of kallikrein preparations or normal plasma fractions resulted in additional activator activity in Fletcher trait plasma which was assessed at 30-40 BAU/ml. This activity was assumed to originate from a previously undescribed plasminogen proactivator whose activation is kallikrein- and factor XII-dependent. Fractionation experiments demonstrated the presence of two major activities and a minor activity caused by kallikrein in normal plasma. It is concluded that plasma kallikrein has two functions in the generation of factor XII-dependent fibrinolytic activity: one as a direct plasminogen activator and another as a factor in the activation of a major factor XII-dependent plasminogen proactivator.
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PMID:Factor XII-dependent fibrinolysis: a double function of plasma kallikrein and the occurrence of a previously undescribed factor XII- and kallikrein-dependent plasminogen proactivator. 48 48

A chromogenic tripeptide - H-D-Val-Leu-Lys-p-nitroanilide-substrate of plasmin, can be used to follow plasminogen activation by an activator such as urokinase or the activator secreted by mouse peritoneal macrophages (thioglycolate-elicited). The acceleration of p-nitroaniline production is proportional to the initial rate of plasmin formation from plasminogen. Thus, at a given plasminogen concentration, this acceleration is proportional to the activator concentration. The acceleration can be evaluated from the spectrophotometer trace recording at 405 nm the appearance of p-nitroaniline, either by means of a computer program or by a plot of delta A405 vs.t2. The sensitivity of this assay allows detection of 0.003 CTA units of urokinase. Thioglycollate-elicited mouse peritoneal macrophages secrete plasminogen activator into the extracellular medium during in vitro cultivation only after a contact with serum.
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PMID:Regulation of plasminogen activator secretion in mouse peritoneal macrophages. I. - Role of serum studied by a new spectrophotometric assay for plasminogen activators. 48 77

Epsilon aminocaproic acid, an inhibitor of plasminogen and trypsinogen activators, can decrease the severity of experimental allergic encephalomyelitis (EAE) in rats. The drug was tried because of a number of observations suggesting that neutral proteases, such as plasmin, might be chemical mediators of demyelination. The highest concentrations of plasminogen activator are found in the walls of veins and venules, around which demyelination is common in many demyelinating diseases, including MS. Indeed, the earliest lesion in MS is often demyelination with little cellular infiltration. In vitro studies have shown that neutral proteases secreted by activated macrophages selectively lyse myelin basic protein.
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PMID:The modification of experimental allergic encephalomyelitis with epsilon aminocaproic acid. 56 43

Neoplastic cells, transformed cells and some normal mammalian cells secrete large amounts of plasminogen activator (PA), an arginine-specific protease which converts plasminogen to plasmin. To study the regulation of PA, we have obtained two classes of mouse-human somatic cell hybrids. PG19, a mouse PA+ cell line, was fused with C32 (human PA+) or human diploid fibroblasts (PA-). All hybrids secreted PA. Human- and mouse-specific forms of PA were distinguished in these hybrids by electrophoretic methods. While all hybrids produced the murine PA, many produced the human PA and some did not. All hybrids which produced human PA had chromosome 6 in common. The absence of each of the other human chromosomes did not affect PA expression, while the absence of chromosome 6 correlated with the lack of human PA. We conclude that chromosome 6 carries the structural gene for human PA. These experiments also show that the fusion of mouse PA+ cells with human PA- cells results in the activation of the human PA gene.
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PMID:Modulation and mapping of a human plasminogen activator by cell fusion. 56 57

The fibrin-agar plate method was used to estimate fibrinolytic activity from the luminal surfaces of aorta and vena cava with or without denudation of endothelium in rabbits. Diffuse endothelial denudation was accomplished by air-dry injury to the luminal surfaces for 24 hours prior to sacrifice. The segments individually obtained from the aorta and vena cava were immediately turned inside out in a cylindrical fashion and soaked in a vial containing plasminogen-rich solution. The vials were kept in a refrigerator at 4 degrees C for 4 hours. Five microliter of the solution was dropped on a fibrin-agar plate containing 0.08% fibrinogen (plasminogen free) and 1.4% agar in 0.01 M phosphate buffer with a pH of 7.4. A thrombin solution was then added to the plates, which were incubated for 18 hours at 37 degrees C in a moist chamber. The fibrinolytically digested areas revealed no comparative difference in fibrinolytic activity between the aorta and the vena cava either in the experimental or control group. However, a plasminogen activator was detected on the luminal surfaces of both the aorta and the vena cava with endothelial denudation as well as in normal controls. These results suggest that luminal fibrinolytic activity may be located not only in endothelial cells but possibly in other sources as well. Further examination of the interaction between the tissue activator and the inhibitor and determination of their localization are needed. Thrombogenesis may be an important factor in atherogenesis; in certain circumstances, detachment of the endothelial cells exposes underlying collagen fibrils and subsequently initiates the aggregation of platelets and cellular proliferation in the intima. There are, however, many unresolved questions concerning the precise mechanisms of development, resolution and organization of thrombi.
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PMID:Measurement of endothelial fibrinolytic activity in aorta and vena cava in rabbits: a fibrin-agar plate method. 57 77

The first (control) group of rabbits breathed ambient air whereas the second was exposed to low level carbon monoxide (CO, 50 ppm by volume) for 24 hr continuously for 8 weeks. The third group was exposed to 300 ppm CO for 4 weeks. The fourth group was exposed to 300 ppm CO for the same period of time as the third group but in addition they were also given epsilon amino caproic acid (EACA) orally, and the results compared to Group III. Per cent oxyhemoglobin (HbO2), per cent hemoglobin (Hb) and per cent carboxyhemoglobin (HbCO) were monitored in all groups. Tests of fibrinolysis were monitored and showed acceleration of the whole blood clot lysis and euglobulin lysis times (ELT). A fibrin plate test confirmed the increased lysis and serum fibrin and/or fibrinogen degradation products (FDP) were elevated in the CO exposed animals. No changes were observed in the same tests in the rabbits exposed to ambient air. The fourth group of animals receiving EACA showed inhibition of lysis and decrease in serum FDP. Alpha-1-antitrypsin and alpha-2-macroglobulin assays in all groups showed no change. Microscopic examination of the large vessels in these test groups showed endothelial damage which indicates a possible source for a plasminogen activator release, or lead to action of Hageman factor and activated plasma plasminogen proactivator.
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PMID:Enhancement of fibrinolysis in rabbits exposed to low and moderate levels of carbon monoxide inhibited by epsilon amino caproic acid. 58 Apr 86

Cell cultures were prepared from nine human brain tumors. Fibrin plate assays showed plasminogen-dependent fibrinolytic activity in lysates and in material released by these neoplastic cells but not in those from normal adult human white matter. Antibodies against human urokinase caused catalytic inhibition of the urokinase and of the plasminogen activator from WI-38 cells, simian virus 40-transformed WI-38 cells, human prostatic cells, and human ovarian carcinoma cells. However, the anti-urokinase immunoglobulin G did not inhibit the plasminogen activator activity of any of the human brain tumor preparations. These studies indicate that the plasminogen activator produced by human brain tumor cells is antigenically different from the plasminogen activator of other human normal and neoplastic cells.
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PMID:In vitro plasminogen activator activity in human brain tumors. 62 Apr 2


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