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

To elucidate the mechanism of synovial damage in rheumatoid arthritis, we studied the activation of latent collagenases released from adherent rheumatoid synovial cells in culture. Latent enzyme was not complexed with alpha2 macroglobulin, the prinicpal proteinase inhibitor in serum, and could be activated by trypsin in the presence of alpha2 macroglobulin if sufficient proteinase was added to saturate inhibitor. Latent collagenase bound half as effectively to collagen fibrils as active enzyme. Plasmin was a threefold better activator of latent enzyme than trypsin and could be generated by addition of plasminogen to synovial-cell cultures. Production of both collagenase and plasminogen activator was inhibited by dexamethasone (10(-9) M). These studies emphasize in importance of control of activation in regulation collagenase activity, It is likely that rheumatoid synovium produces both latent collagenase and plasminogen activator; plasmin is activated from its zymogen, plasminogen, present in inflamed tissues, and in turn activates collagenase.
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PMID:Endogenous activation of latent collagenase by rheumatoid synovial cells. Evidence for a role of plasminogen activator. 6 27

The major plasmin inhibitors namely alpha2-plasmin inhibitor and alpha2-macroglobulin were compared for their effects on lysis of fibrin clot. Plasmin fibrinolytic activity was immediately inhibited by alpha2-plasmin inhibitor, whereas alpha2-macroglobulin inhibited plasmin progressively. Urokinase(plasminogen activator)-induced clot lysis was inhibited efficiently by alpha2-plasmin inhibitor present in the clot. Inhibition of urokinase-induced clot lysis by alpha2-macroglobulin was weak and the molar concentration necessary for alpha2-macroglobulin to achieve the same degree of inhibition as that achieved with alpha2-plasmin inhibitor was about 10 times higher than that of alpha2-plasmin inhibitor. Binding of Lys-plasminogen to fibrin was inhibited by alpha2-plasmin inhibitor but not by alpha2-macroglobulin. Molar concentrations of alpha2-plasmin inhibitor which were effective in inhibiting the binding were 30 times less than that of 6-aminohexanoicacid. alpha2-Plasmin inhibitor was found to interact with Lys-plasminogen to form a weakly-bound complex which is dissociable in the presence of 6-aminohexanoic acid, suggesting that inhibition of binding of Lys-plasminogen to fibrin by alpha2-plasmin inhibitor may be due to interaction of alpha2-plasmin inhibitor with a specific site of the plasminogen molecule and that the site may be 6-aminohexanoic acid-binding site. It is suggested that alpha2-plasmin inhibitor is more reactive and efficient inhibitor of fibrinolysis than alpha 2-macroglobulin.
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PMID:Effects of alpha2-plasmin inhibitor on fibrin clot lysis. Its comparison with alpha2-macroglobulin. 7 50

By the immunofluorescence technique, fibrin, plasminogen and alpha2-macroglobulin demonstrated a similar basic pattern of distribution in the artificial thrombi, rimming the platelet aggregates in the white part and forming a network structure in the red part. The content of plasminogen seemed to be higher in the red part than in the white part. After superfusion with urokinase solution, urokinase was found in a similar pattern of distribution of that of fibrin. The content of urokinase seemed to be higher in the red part, especially in its outer area, than in the white part. It is concluded that urokinase diffused into the artificial thrombi can convert plasminogen, trapped onto fibrin in threads to plasmin. Poor lysibility of the white part might be due to thick strands of fibrin, a low content of plasminogen and a low diffusibility of plasminogen activator, in addition to the antifibrinolytic activity of platelets.
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PMID:Immunofluorescence study on thrombolysis with special reference to the patterns of distribution and the contents of fibrin, plasminogen, alpha2-macroglobulin and urokinase in artificial thrombi. 7 51

The plasminogen activator of the arterial wall was studied with the histochemical method of TODD. The plasminogen activator was removed from the sections after extraction with M-potassium thiocyanate. By this procedure we suggest that the activator demonstrated by the histochemical method is the same substance as that prepared by the extraction method with thiocyanate of ASTRUP and STAGE. However, a new fibrinolytic activity was restored after treatment of these extracted sections with streptokinase or urokinase. There were no differences in the different types of arteries examined and normal or atherosclerotic arteries. Similar findings were found when kidney or myocardial tissues were examined. It is suggested that the arterial and other tissues contain proactivator-plasminogen which is not extracted from the tissue by potassium thiocyanate and can adsorb streptokinase or urokinase.
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PMID:On the nature of fibrinolytic activity of arteries. 7 13

By means of a radio-immunological method the amount of plasminogen activators released by tumours was determined. The concentrations of tumour plasminogen activators was considerably higher in the venous blood of ovarial tumours than in the peripheral blood. In the uterine fluid the uterus cavity the concentration of plasminogen activator was increased in cases with neoplastic endometrium compared to those with normal endometrium.
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PMID:[Tumor plasminogen activators and their clinical significance]. 9 95

Urokinase, the plasminogen activator from human urine, produces a dose-dependent increase in blood flow in the canine superior mesenteric artery when injected intraarterially at doses from 10(-1) to 10(3) units kg-1. This vasodilation persists despite blockade of beta-adrenergic and histamine H1 and H2 receptors as well as inhibition of plasminogen activation, suggesting that these mechanisms are not involved. Infusion of urokinase at 10(2) CTA (Committee on Thrombolytic Agents) units kg-1 min-1 does not produce a sustained vasodilation, but is effective in achieving complete lysis of thrombi within 100 min in the superior mesenteric arterial circulation. Increasing the dose slightly to 125 CTA units kg-1 min-1 results in unwanted clotting abnormalities without attaining a vasodilator level. Decreasing the dose to 75 CTA units kg-1 min-1 still results in complete thrombolysis. In contrast to the results in the femoral circulation, the dose required for fibrinolysis-thrombolysis does not overlap with that for vasodilation in the superior mesenteric artery. Nevertheless, these experiments provide some basis for the use of intraarterial urokinase infusion in the treatment of nonocclusive mesenteric ischemia and, perhaps, thrombotic occlusion of the superior mesenteric artery.
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PMID:Vasodilation, fibrinolysis, and thrombolysis with intraarterial infusion of urokinase in the canine superior mesenteric artery. 9 90

The assay of plasminogen activator activities on fibrin plates was re-evaluated with special reference to fibrinolysis inhibitors present in samples and in fibrin plates. The nature, action and stability of inhibiting material were studied in tissue with considerable differences in activator and inhibitor contents: human lung, liver and placenta. Extracts were tested for inhibitory capacity against purified human uterine tissue plasminogen activator, urokinase and plasmin of fibrin plates prepared from different grades of fibrinogen and fibrin. The tissue extracts inhibited fibrinolysis on fibrin plates to varying degrees, dependent on the sample medium, the type of fibrin plate and the kind of plasminogen activator. The influence of inhibitors in the sample and in the fibrin plate was partly abolished by the presence of 2 M KSCN in the sample. The procedure for preparing the samples as described by Astrup and Albrechtsen did not completely eliminate the inhibitory action against the added plasminogen activators. Comparison of urokinase inhibition with tissue activator inhibition by the tissue extracts as to the degree of denaturation in the Astrup and Albrechtsen procedure showed that they have much in common. Nevertheless, some differences were found which indicated the possible existence of separate urokinase and tissue activator inhibitors or of different inhibition mechanisms for these plasminogen activators.
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PMID:Interfering factors in the assay of plasminogen activators by the fibrin plate method. Occurrence of different inhibitors against tissue plasminogen activator and urokinase. 11 68

Component levels of the fibrinolysin system in the plasma and ascitic fluid of Swiss mice bearing Ehrlich ascites tumor cells were determined during a 15-day tumor growth time phase. During tumor growth, the concentration of plasminogen in the ascitic fluid decreased inversely to the total packed cell volume. Free plasmin was not present in the ascitic fluid nor was there any measurable plasminogen activator activity. Both antiplasmin activity and fibrinogen levels present in the fluid decreased during tumor growth. The nuclear and mitochondrial-microsomal subcellular fractions of the tumor cell exhibited plasminogen activator activity. No significant changes in the above parameters occurred in the plasma during the tumor growth period we studied.
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PMID:Proteases during the growth of Ehrlich ascites tumor. I. The fibrinolysin system. 12 66

Fibrinolysic cadaveric blood studied after a rapid death (strangulation asphyxia, traumatic and sudden death) contained no plasmin--an enzyme of fibrin destruction, and no plasminogen--its inactive precursor. In the absence of plasmin and plasminogen of interest is a high content of plasminogen activator. An increase in the content of the activator in the fibrinolysic blood exists along with a marked proactivator level. A relationshp between the concentration of the activator and the proactivator in this blood indirectly pointed to the intravascular (from the pre-existing blood proactivator of the living), and not the tissue origin of the activator. Activation of plasma proactivator is caused by the entrance of tissue lysokinases into the circulation.
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PMID:[Postmortem fibrinolysis and its biological characteristics]. 12 29

The effect of a cadaver-derived vascular plasminogen activator (VA) on the degradation of fibrinogen, soluble fibrin monomer, and fibrin was studied and compared with the effect of equivalent fibrinolytic potencies of streptokinase (SK), urokinase (UK), and plasmin. The proteolytic activity of the three activators and plasmin was determined by a standard fibrin plate assay and was expressed in CTA units from a UK reference curve. Fibrinogen degradation was measured by clottable protein determinations and by an electrophoretic technique sensitive to small changes in the molecular weight of fibrinogen. When VA was incubated in plasma, no degradation of fibrinogen occurred, whereas rapid fibrinolysis took place after the plasma was clotted. By contrast, equivalent potencies of SK, UK, and plasmin caused extensive fibrinogenolysis. Since the plasmin added and that formed by the three activators had equivalent fibrinolytic activity, the failure of VA to induce fibrinogen degradation was attributed to antiactivators rather than antiplasmins. VA activity in plasma was consumed by clotting, whereas the antiactivator activity remained in the serum, suggesting dissociation of the VA-antiactivator complex on the fibrin clot. Fibrinogen and its soluble derivatives resisted degradation by VA in plasma because a solid phase appeared necessary for the complex to dissociate. The findings indicated that the degradation of fibrinogen or soluble fibrin in blood as a result of plasminogen activation by VA was unlikely to occur due to a large excess of antiactivator activity. Alternative pathways for their catabolism are discussed.
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PMID:The resistance of fibrinogen and soluble fibrin monomer in blood to degradation by a potent plasminogen activator derived from cadaver limbs. 12 95


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