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)

Monocytes and monocytoid cell lines previously have been shown to express receptors for plasminogen and urokinase (u-PA). In the present study, the monocytoid cell lines, U937 and THP-1, are shown to bind tissue plasminogen activator (t-PA) in a specific, saturable, and reversible manner. These cells bound t-PA with low affinity (kd = 0.67 to 0.97 mumol/L) and high capacity (0.71 to 3.3 x 10(6) receptors/cell). Human peripheral blood monocytes bound t-PA with a kd (0.9 mumol/L) similar to that of the monocytoid cells but with a lower capacity (0.17 x 10(6) sites/cell). These binding parameters also were similar to the low-affinity interaction of t-PA with endothelial cells as measured with the cells in suspension (kd = 0.73 mumol/L and 1.1 x 10(6) sites/cell). Lysine analogues and active or diisopropylfluorophosphate-inactivated u-PA inhibited t-PA binding to monocytes, monocytoid cells, and endothelial cells with similar IC50 (concentration producing 50% inhibition) values, suggesting that the same recognition specificity mediates t-PA binding to all of these cell types. The existence of a high-affinity binding site for t-PA on monocytoid cells was also explored in detail. Unlike endothelial cells where plasminogen activator inhibitor-1 has been implicated in mediating a high-affinity interaction of t-PA with the cells, no evidence for a role of this inhibitor in ligand binding to the monocytoid cells was found. Furthermore, using both high and low 125I-t-PA concentrations, competition analyses with lysine analogues or u-PA, or treatment of the cells with carboxypeptidase B, failed to indicate the presence of distinguishable classes of t-PA binding sites. In sum, low-affinity receptors for t-PA are expressed at high density on monocytes and monocytoid cells, identifying a new element in the fibrinolytic arsenal of these cells.
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PMID:Binding of tissue plasminogen activator to human monocytes and monocytoid cells. 193 47

Interleukin-1 (IL-1) release from monocyte-macrophages (Mo) appears dependent on pericellular proteolysis mediated by plasmin. Thus plasminogen activator inhibitors (PAI) which bind the serine proteases responsible for the conversion of plasminogen to plasmin, may inhibit IL-1 release from Mo. We have examined the effect of purified PAI from a hepatoma cell line Hep G2, on IL-1 release from Mo with secondary effects on lymphocyte proliferation in vitro. Fast acting inhibitors of both urokinase (u-PA) and tissue plasminogen activator (two chain t-PA) were noted in harvest fluids of Hep G2 cells. These inhibitors were stable at pH 3 but lost activity at 45 degrees C. They were SDS-stable and migrated with Mr53 and 104 kDa. These properties conformed to characteristics of type-1 plasminogen activator inhibitor (PAI-1). Partially purified PAI-1 added to human Mo cultured on 125I fibrin layer both in the presence and absence of plasminogen inhibited secretion of IL-1 by Mo in response to LPS. This effect, however, did not correlate with the inhibition of plasminogen dependent fibrinolysis. This suggested a degree of sequestration and inaccessibility of membrane bound u-PA of LPS activated Mo to PAI-1. PAI-1, in addition, inhibited mitogen stimulated peripheral blood mononuclear cell (PBMC) proliferation at similar concentration ranges. This effect was abrogated by the addition of specific antisera to PAI-1. PAI-1 may be released as part of an acute phase response. In addition to influencing fibrinolysis, PAI-1 may constitute a negative feedback pathway on Mo IL-1 release and subsequent immune activation in vivo.
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PMID:Monocyte-macrophage release of IL-1 is inhibited by type-1 plasminogen activator inhibitors. 196 70

Levels of major parameters of fibrinolysis were measured in 50 normal human fetuses between 19 and 39 weeks of gestation and compared to those of 50 healthy normal pregnant women and 30 adult controls. In fetuses, euglobulin clot lysis time (ECLT) was significantly shortened, plasminogen level was low and histidine-rich glycoprotein undetectable. While t-PA and u-PA levels were slightly lower than in adult controls, a significant decrease in PAI activity was demonstrated and no PAI-2 could be detected in fetal plasma. In contrast with these findings, the fibrinolytic equilibrium of pregnant women exhibited a prolonged ECLT and a strong increase in both PAI activity and PAI-2 antigen levels, while only a moderate elevation in u-PA and t-PA levels was measured.
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PMID:Comparative study of the fibrinolytic system in human fetuses and in pregnant women. 202 51

In 22 human tumor cell lines the regulation of production of plasminogen activators urokinase (u-PA) and tissue-type (t-PA) and their inhibitors PAI-1 and PAI-2 was studied. These four components may determine the net plasminogen activator activity, which is often associated with tumor development and metastatic processes. The amount of specific mRNA and protein produced by the cells was measured for all four components. The frequent finding of t-PA (alone or in combination with u-PA) suggests that t-PA can also be a tumor-associated plasminogen activator. In 11 of the 22 cells PAI-1 mRNA and in 6 of the 22 cells PAI-2 mRNA was found, pointing to a possible role of plasminogen activator inhibitors in the tumor-related plasminogen activator activity. This study demonstrates that there are at least two important regulatory steps in the regulation of production of plasminogen activators and their inhibitors: (a) the regulation at the mRNA level, since a high protein amount is always correlated with a high mRNA amount found in the tumor cells; (b) there must be a significant regulatory step at the (post)translational level as can be concluded from differences in mRNA usage.
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PMID:Protein and messenger RNA levels of plasminogen activators and inhibitors analyzed in 22 human tumor cell lines. 210 39

The persistency of fibrin deposits in the kidney during renal diseases could reflect either a defective release of plasminogen activators (PA) or a local excess of PAI. In order to investigate this question, we studied human renal biopsies by immunofluorescence technique with specific antibodies for fibrin, tissue-type plasminogen activator (t-PA), urokinase (u-PA), PAI-1 and PAI-2. By this technique t-PA could be detected in the glomerular flocculus and the endothelium of small arteries of the normal control kidneys. We failed to detect significant fluorescence with other antibodies in normal kidneys. Conversely, in cases of vascular nephropathy with thrombosis the positive fluorescence obtained with anti-fibrin antibodies at the site of thrombosis was associated with a positive fluorescence with anti-PAI-1 and to a lesser extent with anti-t-PA antibodies. u-PA and PAI-2 were not detected in these lesions. Similarly in the most severe forms of crescentic glomerulonephritis, extracapillary fibrin deposits were associated with PAI-1. In one case u-PA was also detected. This is in agreement with our previous findings that glomerular epithelial cells release both PAI-1 and the inactive form of u-PA (pro u-PA). Thus, our results support the hypothesis that PAI-1, which is able to inhibit both t-PA and u-PA, may play a major role in the persistency of fibrin deposits in the human kidneys during pathological conditions.
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PMID:Plasminogen activator inhibitor 1 in renal fibrin deposits of human nephropathies. 210 50

Plasminogen activator inhibitor-type 1 (PAI-1) was identified in extracts of Lewis lung carcinoma, and its immunohistochemical localization was studied together with that of urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators. All primary tumors (n = 11) contained heterogeneously distributed immunoreactivity against each of the three components. Most often, areas that contained u-PA immunoreactivity also contained PAI-1 immunoreactivity. However, several areas showed a strong u-PA immunoreactivity, but no or low PAI-1 immunoreactivity. The latter staining pattern was only found in peripheral areas, and usually in areas with histological signs of tissue destruction. Lung metastases always contained u-PA immunoreactivity, while PAI-1 immunoreactivity was found in most, but not all, metastases. t-PA immunoreactivity was found in a few scattered tumor cells, in primary carcinomas as well as metastases. Controls that included absorption with highly purified antigen preparations and immunoblotting, indicated that all the immunoreactivity represented genuine PAI-1, u-PA and t-PA, respectively. The results are consistent with an assumption that the plasminogen activation system, and particularly u-PA and PAI-1, plays a role in regulation of breakdown of extracellular matrix proteins during invasive growth in this carcinoma.
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PMID:Plasminogen activator inhibitor-type 1 in Lewis lung carcinoma. 210 45

Intra-alveolar fibrin deposition is one of the pathological hallmarks of acute lung injury. Because alveolar epithelial cells play a central role in the repair process following acute lung injury, this study was undertaken to examine their potential to produce a plasminogen activator (PA). We now report the synthesis and secretion of PA by rat alveolar epithelial cells with the catalytic properties of a urokinase-type (u-PA) rather than tissue-type plasminogen activator. Studies of regulation of epithelial cell u-PA revealed: 1) phorbol myristate acetate (PMA) but not the inactive structural analog 4 alpha-PMA upregulated u-PA synthesis, putatively via the protein kinase C pathway; 2) PMA induction of u-PA activity was substantially inhibited by dexamethasone and completely inhibited by cycloheximide; 3) unstimulated alveolar epithelial cells had no detectable u-PA mRNA, whereas PMA exposure led to activation of the u-PA gene and accumulation of a 2.5-kilobase u-PA mRNA; and 4) cycloheximide did not abolish this induction of u-PA mRNA suggesting that intermediate protein synthesis was not necessary for the activation of transcription. In light of their capacity to promote fibrinolysis and their strategic anatomic location, alveolar epithelial cells are likely to play a key role in the extensive remodelling process that follows acute lung injury.
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PMID:Alveolar epithelial cell plasminogen activator. Characterization and regulation. 211 May 65

The fibrinolytic activity (FA) has been studied on the synovial membrane obtained from 16 patients with osteoarthritis (OA), 20 patients with rheumatoid arthritis (RA) and 11 control subjects. Todd's autohistographic method, modified by Lotti, was used to investigate the FA and the monoclonal antibodies against u-PA and t-PA were used to identify the main plasminogen activator. Our results show that the FA is increased in the synovial membrane of patients with OA in comparison with the synovial FA of control subjects. In the synovial membranes from patients with RA, the FA shows different results: in some specimens FA is increased, and in others it is diminished or similar, compared with FA of samples from healthy controls. Thus, our data on synovial FA in OA confirm the previous reports, performed in vitro, on the activation of the plasmin system in this degenerative disease. The activity of the fibrinolytic system seems to participate in the cartilage degeneration and, via the activation of collagenase, to perpetuate the cartilage damage.
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PMID:Fibrinolytic activity in the synovial membrane of osteoarthritis. 211 5

Changes in plasminogen activator (PA) and PA inhibitor (PAI) activities were measured during follicular development in granulosa cells (GC) and theca tissue (TT) isolated from the six largest yolk-filled preovulatory follicles (F1, F2, F3, F4, F5, F6) and large white follicles (LWF) of the domestic hen. PA activity increased and PAI activity decreased during follicular development, with the peak PA value and minimum activity for PAI observed in the largest preovulatory follicle (F1) 12-14 h before expected time of ovulation. The PA activity in GC and TT appears to be principally of the tissue (t)-PA type judging from its substrate specificity and biochemical characteristics. The enzyme cleaved the chromogenic substrate specific for t-PA (Spectrozyme TM t-PA; CH3SO2-D-CHT-Gly-Arg-p-nitroanilide) more efficiently (4-6 x) than that for u-PA (Spectrozyme TM UK; Cbo-L-Glu-(alpha-t-BuO)-Gly-Arg-p-nitroanilide), suggesting that t-PA may be the predominant PA in the chicken preovulatory follicle. Determination of PA activity following sodium dodecyl sulphate-polyacrylamide gel electrophoresis and isoelectric focussing suggested the presence of two forms of the enzyme in GC and TT. The predominant form of PA had a molecular weight of 75,000 and an isoelectric point (pI) of 7.7, characteristics similar to those reported for t-PA in humans, pigs, and rodents. The other form of PA had a molecular weight of 35,000 and pI of 8.4. PAI present in GC and TT had a molecular weight of 50,000 and pI of 4.7. In GC, an acid-labile PAI was detected with biochemical characteristics similar to those of the protease, nexin I.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in tissue-type plasminogen activator-like and plasminogen activator inhibitor activities in granulosa and theca layers during ovarian follicle development in the domestic hen. 211 20

The tissue-specific distribution of tissue-type and urokinase-type plasminogen activator (t-PA and u-PA) and their inhibitor type 1 (PAI-1) was analyzed at mRNA level in five major rat organ tissues. t-PA mRNA was detected in lung, kidney, heart, and liver. u-PA mRNA was detected in kidney and lung. Presence of PA mRNA correlated with the detection of PA activity in extracts of these tissues. PAI-1 mRNA was detected predominantly in heart and lung. Although PAI activity could not be measured directly in tissue extracts, the presence of PAI-1 mRNA correlated with the occurrence of PA.PAI complex in fibrin autography of tissue extracts. Endotoxin injection caused a very large increase in plasma PAI activity. This increase correlated with a marked increase in PAI-1 mRNA in nearly all tissues studied. The increase in PAI-1 mRNA is most pronounced in lung and liver. Endotoxin injection also caused an increased level of t-PA mRNA in heart and kidney, and an increased u-PA mRNA level in kidney. mRNA analysis of freshly isolated and separated subfractionated liver cells showed that the marked increase in PAI-1 mRNA in the liver after endotoxin injection may be due mainly to a strong increase of PAI-1 mRNA in the liver endothelial cells.
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PMID:Endotoxin induction of plasminogen activator and plasminogen activator inhibitor type 1 mRNA in rat tissues in vivo. 211 27


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