Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interface tissues and pseudocapsules from loose total hip replacements were removed during revision of 11 cases and were investigated for the plasminogen activation system and IL-1beta. Control samples of synovium were taken during knee arthroscopy (n 8), and from the hip joint during primary total hip replacement (n 5). The concentrations of urokinase plasminogen activator (uPA), tissue type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and interleukin 1beta were all found to be significantly different in interfaces and in pseudocapsules, compared to controls. Immunohistochemistry disclosed localization in periprosthetic tissues of uPA, uPA-receptor and tPA in macrophages with phagocytosed metal, polyethylene, cement particles or accompanying pieces of necrotic bone. PAI-1 staining was present in the neighboring areas that stained for uPA or tPA, but PAI-1 staining was also found overlapping and outside these areas. These findings suggest a role for the uPA/uPA- receptor and PAI-1 in activation and focalization of extracellular matrix degradation in periprosthetic tissues. The expression of the plasminogen activation system by macrophages containing phagocytosed material suggests undegradable microdebris as a possible initiating and perpetuating stimulus for a proteolytic activation cascade, which may contribute to loosening of the prosthesis.
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PMID:The plasminogen activation system is upregulated in loosening of total hip prostheses. 862 68

During acute exercise both coagulant and fibrinolytic potential increase. Since strenuous exertion is associated with an enhanced risk for cardiac events, especially in untrained individuals, it is important to determine whether the initial haemostatic balance is maintained during exercise. Twenty-nine sedentary males (20-30 years) were subjected to a standardized cycle ergometer test. Blood samples were obtained at two exercise levels, 70% VO2max (submaximal), 100% VO2max (maximal) and during 25 min recovery. Both during submaximal and maximal performance, tissue type plasminogen activator antigen, urokinase plasminogen activator antigen and tissue type plasminogen activator activity were increased. A concomitant enhancement of clotting activity of factors VII, VIII, IX, XII and fibrinogen resulted in a shortening of clotting times. Following correction for changes in plasma volume, the results for factor VII:c were reversed, and factor XII:c and fibrinogen no longer demonstrated exercise-related changes. Increases in coagulant (activated partial thromboplastin time) and fibrinolytic (tissue type plasminogen activator activity) potential proceeded in parallel during exercise. However, during recovery while there was a sustained increase in coagulant potential, fibrinolytic potential demonstrated a sharp fall. We conclude that during physical activity, while parallel changes in coagulant and fibrinolytic activity occur, this haemostatic balance is not maintained during recovery. This phenomenon could constitute an enhanced risk for coronary artery thrombosis which may contribute to exercise-related cardiovascular events.
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PMID:Unbalanced haemostatic changes following strenuous physical exercise. A study in young sedentary males. 868 38

In order to reach the sites of inflammation, lymphocytes leave the bloodstream and migrate into peripheral tissues, in a process involving integrin-mediated adhesion to the vascular endothelium, followed by transmigration across the endothelial barrier and through the underlying interstitial matrix. We have investigated the role of the plasminogen activator/plasmin system in normal T cell migration. Receptors for urokinase plasminogen activator (uPAR) were not expressed in resting T lymphocytes, but could be efficiently induced at the mRNA and protein level by coclustering of the antigen receptor complex and beta1 or beta2 integrins, through a signalling pathway involving both protein kinase C activation and an increase in intracellular cyclic AMP. Catalytic activation of plasminogen by uPAR-expressing T cells promoted their migration through an extracellular matrix in vitro. Plasmin-induced invasion was inhibited by plasmin-and urokinase inhibitors and by anti-uPAR antibodies. Finally, cytofluorimetric and immunohistochemical analysis of primary human tumor specimens showed the presence of uPAR positive infiltrating T cells in vivo. Collectively, these findings suggest that plasminogen activation may play a role in lymphocyte migration in vivo, and that integrin-dependent expression of membrane-associated endopeptidases could represent an additional step in the regulated process of leukocyte transmigration.
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PMID:Integrin-dependent induction of functional urokinase receptors in primary T lymphocytes. 878 76

Several tissue remodeling events that require extracellular proteolysis are thought to be mediated by plasminogen activators that convert the inactive proenzyme plasminogen to active plasmin. The involvement of plasminogen activator in many biological phenomena reflects the ubiquitous presence of plasminogen and the ability of numerous cell types to synthesize plasminogen activator in a highly regulated manner. Increased plasmin and plasminogen activator in bovine milk are correlated with gradual involution (the declining phase of lactation). Treatment with bST prevented the increase in plasmin during gradual involution, indicating that bST interferes with conversion of plasminogen to plasmin. Concentrations of plasminogen activator in mammary tissue are high after cessation of milking. These results reinforce the association of the plasmin-plasminogen system with gradual involution postlactation. Recently, a role has been proposed for plasminogen activator in cell proliferation in several cellular systems. Insulin and IGF-I increased synthesis of urokinase plasminogen activator and enhanced proliferation of cultured bovine mammary epithelial cells. In contrast, phorbol myristate acetate, which increased expression of urokinase plasminogen activator mRNA by mammary epithelial and myoepithelial cells, stimulated proliferation of myoepithelial cells, but not epithelial cells. Thus, expression of plasminogen activator is not simply related to mitogenesis but is likely to serve multiple functions in bovine mammary epithelial cells.
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PMID:Plasminogen activator system: implications for mammary cell growth and involution. 882 75

Nineteen patients with symptoms of chronic venous insufficiency (CVI) were treated with 13-week cycles of intermittent pneumatic compression (IPC) during 2 h sessions twice weekly, with most treatments at home. At study completion, quantitative subjective scores for total symptomatology were improved in 16/19 patients (84%). Enhancement of fibrinolytic potential in vivo was detected in 86% of observations on specimens from CVI patients over 2 h of IPC, with accelerated euglobulin clot lysis times (ELT) noted within 15 min of initiating compression. The enhanced fibrinolytic potential was attributed to increased urokinase plasminogen activator (u-PA), probably released from perturbed endothelial cells by IPC. Significant decreases in total t-PA antigen (mass concentration) but not t-PA activity, were produced by IPC in CVI patients only (P = 0.0001), with greater effects noted in the non-anticoagulated versus the anticoagulated cohort. Plasminogen activator inhibitor type 1 (PAI-1) levels rose rapidly after IPC only in the controls and non-anticoagulated CVI patients. PAI-1 decreased in those receiving anticoagulation. No platelet perturbation was detected during IPC by measuring levels of beta-thromboglobulin or the thromboxane A2 metabolite, 11-dehydrothromboxane B2; however, significant (P < 0.003) decreases in plasma prostacyclin (PGI2) levels (measured as the stable 6-ketoprostaglandin F-1-alpha-metabolite) were observed after 15 min of IPC in non-anticoagulated CVI patients only. There was no evidence of increased thrombin generation by IPC, determined by urinary excretion of fibrinopeptide A and prothrombin fragment 1. Concurrent anticoagulation appears to mediate more favorable biochemical alterations in CVI, although subjective improvement did not correlate with anticoagulation. The mechanism(s) by which these physiologic changes compliment the mechanical effects of IPC remain to be elucidated and will require adequately controlled and powered studies.
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PMID:Intermittent pneumatic compression in chronic venous insufficiency favorably affects fibrinolytic potential and platelet activation. 883 95

The effect of transforming growth factor-beta (TGF-beta) was analyzed on the synthesis of fibronectin, collagen type IV, and urokinase plasminogen activator in human glomerular epithelial cells in culture. An increase in the abundance of specific mRNA was found for collagen type IV and fibronectin. Fibronectin protein synthesis was also increased in TGF-beta treated cells; most of the de novo synthesized fibronectin was found as an unsoluble protein associated with extracellular matrix. In the same cells the amount of plasminogen activator mRNA was found leading also to a decreased surface expression of urokinase plasminogen activator. The data support the concept that by upregulating matrix protein synthesis and downregulating the plasminogen activator system, TGF-beta favors the development of sclerosis.
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PMID:Interaction of transforming growth factor beta 1 with human glomerular epithelial cells in culture: opposite effects on synthesis of matrix proteins and on urokinase plasminogen activator. 884 65

The expression of components of the plasminogen activator system was investigated in patients with oesophageal carcinoma. Tumour and normal mucosa were obtained from resected oesophageal carcinomas and antigens were measured by enzyme-linked immunosorbent assay. Median levels of urokinase plasminogen activator (uPA) and the uPA receptor were higher in carcinoma than in matched normal mucosa (squamous cell carcinoma: uPA 4.05 versus 0.66 ng antigen per mg protein, uPA receptor 1.95 versus 0.50 ng/mg, n = 10, P < 0.05; adenocarcinoma: uPA 2.16 versus 0.61 ng/mg, uPA receptor 2.01 versus 0.49 ng/mg, n = 8, P < 0.05). Tissue plasminogen activator (tPA) level was lower than control values in squamous cell carcinoma but not in adenocarcinoma (1.97 versus 4.70 ng/mg, P < 0.05). There was no difference in plasminogen activator inhibitor (PAI) 1 level between carcinoma and normal mucosa. The PAI-2 level was lower than that in normals in adenocarcinoma only (6.0 versus 64.77 ng/mg, P < 0.05). These data support the hypothesis that membrane-bound uPA has a role in the breakdown of extracellular matrix in invasive oesophageal carcinoma.
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PMID:Plasminogen activators in oesophageal carcinoma. 886 32

The concentrations of matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-8 (MMP-8), matrix metalloproteinase-9 (MMP-9), lactoferrin and urokinase plasminogen activator (uPA), tissue-type plasminogen activator (tPA) and the inhibitors, tissue inhibitor of metalloproteinase-1 (TIMP-1), plasminogen activator inhibitor-1 (PAI-1), plasminogen activator inhibitor (PAI-2), and alpha2-macroglobulin in the synovial fluids of patients with rheumatoid arthritis was determined before and during chemical synoviorthesis with a sodium salt of the fatty acids from cod-liver oil (Varicocid). Synovial fluids were obtained before treatment from 37 patients with rheumatoid arthritis and, in most cases, at 8 and 24 h after injection of the agent. Well-established ELISAs were used to determine the amounts of all proteins. All patients with rheumatoid arthritis revealed very high levels of metalloproteinases (about 1-15 mu g/ml) in their synovial fluids. During the inflammation inducing treatment the granulocyte enzymes increased. In contrast to this, the level of MMP-1 decreased. All granulocyte-derived enzymes were strongly correlated with each other, whereas their dependence on the granulocyte count was only weak. uPA and PAI-2 showed good correlations with the granulocytes-derived enzymes, but were also only weakly correlating with the cell counts. t-PA was not detected by the ELISA used. The proteases, MMP-8, MMP-9 and uPA were increased 8 h after the treatment, whereas the specific inhibitors TIMP-1, PAI-1 and PAI-2 showed significant changes only 24 h after the injection. Matrix metalloproteinases are important factors in the pathogenesis of rheumatoid arthritis. The inflammatory activity in the joint could be better correlated to the granulocyte enzymes than to the granulocyte counts. The levels of uPA and PAI-2 are also parallel to the granulocyte enzyme levels and might underly the same regulatory mechanism.
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PMID:Determination of metalloproteinases, plasminogen-activators and their inhibitors in the synovial fluids of patients with rheumatoid arthritis during chemical synoviorthesis. 891 99

Thrombolytic therapy has not been widely used for pulmonary embolism due to less than optimal results with conventional plasminogen activators. We propose a new approach to deliver plasminogen activators to the luminal surface of the pulmonary vasculature to potentially improve dissolution of pulmonary thromboemboli. Our previous studies have documented that a monoclonal antibody (mAb) to angiotensin-converting enzyme (anti-angiotensin-converting enzyme mAb 9B9) accumulates in the lungs of various animal species after systemic administration. We coupled 125I-labeled biotinylated plasminogen activators (single-chain urokinase plasminogen activator, tissue-type plasminogen activator and streptokinase) to biotinylated mAb 9B9, using streptavidin as a cross-linker. The fibrinolytic activity of plasminogen activators was not changed significantly by either biotinylation or by coupling to streptavidin. Antibody-conjugated plasminogen activators bind to the antigen immobilized in plastic wells and provide lysis of fibrin clots formed in these wells. Therefore, antibody-conjugated plasminogen activators bound to their target antigen retain their capacity to activate plasminogen. One hour after i.v. injection of mAb 9B9-conjugated radiolabeled biotinylated single-chain urokinase plasminogen activator, biotinylated tissue-type plasminogen activator or biotinylated-streptokinase in rats, the level of radiolabel was 7.4 +/- 0.8, 5.9 +/- 0.4 and 3.6 +/- 0.4% of injected dose/g (ID/g) of lung tissue vs. 0.5 +/- 0.01, 0.3 +/- 0.01 and 0.6 +/- 0.3% ID/g after injection of the same activators conjugated with control mouse IgG (P < .01 in all cases). Injection of mAb 9B9-conjugated radiolabeled plasminogen activator led to its rapid pulmonary uptake with a peak value 6.2 +/- 1.2% ID/g attained 3 hr after injection. One day later, 2.2 +/- 0.5% of the injected radioactivity was found per gram of lung tissue, although the blood level was 0.13 +/- 0.03% ID/g (lung/blood ratio 16.7 +/- 0.3). Therefore, conjugation of plasminogen activators with anti-angiotensin-converting enzyme mAb 9B9 provides their specific targeting to and prolonged association with the pulmonary vasculature. These results provide a basis for study of the local pulmonary fibrinolysis by mAb 9B9-conjugated plasminogen activators.
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PMID:Targeting of antibody-conjugated plasminogen activators to the pulmonary vasculature. 893 Feb 13

Serosal trauma elicits an inflammatory response which leads to the deposition of fibrin at injured sites, the residuals of which appear to be essential in excessive tissue repair and formation of intraabdominal adhesions. Local plasminogen activity may modulate this early phase of tissue repair. The present study was undertaken to investigate the distribution and cellular expression of plasminogen activators and their inhibitors in human peritoneal normal and inflamed tissue. Tissue-type plasminogen activator (t-PA) was expressed in subserosal capillary walls, and in normal mesothelium, but not in inflammation. Immunoreactivity for the plasminogen activator inhibitor type 1 (PAI-1) was present in normal mesothelium, and substantially increased in inflammation, where, in addition, immunoreactivity was found throughout the submesothelial tissue. This PAI-1 was partly co-localized with macrophages, as was the urokinase plasminogen activator (u-PA), suggesting an involvement of these cells in peritoneal tissue fibrinolysis. Inflammation or abrasion of the mesothelium during surgery is likely to cause a depletion of the local t-PA source and expose the potentially PAI-1-containing submesothelial tissue, thus promoting persistence of fibrin and formation of adhesions.
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PMID:Plasminogen activators and inhibitors in peritoneal tissue. 906 97


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