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

Human tear fluid has plasminogen activator activity. The type of plasminogen activator activity in unstimulated and stimulated tears was determined, using antibodies that specifically neutralize tissue plasminogen activator or urokinase. All plasminogen activator activity was tissue plasminogen activator-related in both types of tears. Correlations between activities of beta-hexosaminidase, lysozyme and lactate dehydrogenase with tissue plasminogen activator activity indicate that the contribution to plasminogen activator activity of conjunctival and corneal epithelium is more important in unstimulated tears than stimulated tears. In stimulated tears the tissue plasminogen activator activity originates mainly from the lacrimal gland. It is suggested that a constant concentration of plasminogen activator is released from the lacrimal gland and that this concentration is independent of the secretion rate of tear fluid and that the release from the conjunctiva is due to desquamation of cells.
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PMID:Immunological characterization and possible origin of plasminogen activator in human tear fluid. 668 45

The effect of the cyclooxygenase inhibitors, indomethacin and diclofenac, and of PGE2 on either resting or stimulated macrophages was investigated. Peritoneal macrophages were obtained from untreated mice and cultured for 10 days. Macrophage activation was induced by zymosan phagocytosis and was monitored by testing for plasminogen activator secretion and the cellular levels of lactate dehydrogenase, beta-glucuronidase and alkaline phosphodiesterase I. It was found that cyclooxygenase inhibitors activate resting macrophages and enhance the degree of activation obtained after zymosan phagocytosis. Addition of exogenous PGE2, on the other hand, had the opposite effect, it suppressed activation induced either by cyclooxygenase inhibitors, phagocytosis or a combination of both. Cyclooxygenase inhibitors and PGE2 did not affect the hexose monophosphate shunt activity of resting macrophages and had only a minor effect on the respiratory burst occurring during zymosan phagocytosis. It appears, therefore, that the observed changes in the state of activation of the macrophages are not related to hexose monophosphate shunt activity. The described effects suggest that PGE2 and possibly other cyclooxygenase products may function as inhibitory feed-back regulators of macrophage activation.
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PMID:Effects of cyclooxygenase inhibitors and prostaglandin E2 on macrophage activation in vitro. 679 85

We studied the significance of tissue-type plasminogen activator (tPA) on the pretransplant assessment of liver graft viability in rats. The liver grafts were excised from the rats and then divided into two groups. Group 1 consisted of grafts preserved for 4 h in chilled, lactated Ringer's solution (4 degrees C) and group 2 consisted of grafts preserved for 6 h in the same solution. After preservation, the liver grafts were flushed out through the portal vein using 5 ml of chilled, lactated Ringer's solution (4 degrees C). The entire effluent from the hepatic veins was then collected and analyzed for tPA, ammonia, lactate, pyruvate, glutamic oxaloacetic transaminase, and lactate dehydrogenase. The tPA concentration of effluent in group 2 was significantly higher than that in group 1 (0.80 +/- 0.23 ng/ml vs 0.42 +/- 0.08 ng/ml, P < 0.05). The lactate, pyruvate, and ammonia levels in group 2 were also higher than those in group 1 (134 +/- 13 mg/dl vs 120 +/- 2 mg/dl, 0.34 +/- 0.40 mg/dl vs 0.09 +/- 0.01 mg/dl, and 183 +/- 79 micrograms/dl vs 102 +/- 40 micrograms/dl, respectively). However, the discriminative power of tPA was stronger than that of the other parameters. Histological findings revealed a higher number of trypan blue-stained sinusoidal lining cells that were detached and swollen in group 2. We conclude that the amount of tPA in the effluent flushed from the graft can serve as a sensitive and reliable indicator of cold-preserved liver grafts in rats.
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PMID:The significance of tissue-type plasminogen activator for pretransplant assessment of liver graft viability: analysis of effluent from the graft in rats. 791 20

Since basic fibroblast growth factor (bFGF) modulates the functions of vascular endothelial cells, we hypothesized that this factor may be involved in the regulation of the blood coagulation-fibrinolytic system mediated by the cells. Confluent cultures of vascular endothelial cells from human umbilical vein were treated with recombinant human bFGF (bFGF) in a serum-free medium and the content of tissue plasminogen activator antigen (t-PA:Ag) in the medium was determined by EIA. Treatment with bFGF resulted in a significant decrease in the release of t-PA:Ag from the cells accompanied with a less t-PA activity in the medium. In contrast, the t-PA:Ag release from human aortic endothelial cells was significantly increased by bFGF. The bFGF-induced decrease in the t-PA:Ag release from the venous endothelial cells was completely blocked by anti-bFGF antibody. The incorporation of [3H]leucine into the acid-insoluble fraction of the cells was significantly increased by bFGF; however, the activity of lactate dehydrogenase leaked into the medium was significantly decreased, suggesting that the suppression of the t-PA:Ag release caused by bFGF in the venous endothelial cells was not due to either a nonspecific inhibition of protein synthesis or a nonspecific cell damage. Since bFGF is postulated to be released from damaged endothelial cells, the present data suggest the regulation by bFGF of hemostasis mediated by endothelial cells when the vascular endothelium was damaged.
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PMID:Basic fibroblast growth factor suppresses tissue plasminogen activator release from cultured human umbilical vein endothelial cells but enhances that from cultured human aortic endothelial cells. 819 18

Administration to rats of monocrotaline pyrrole (MCTP), a putative metabolite of the pyrrolizidine alkaloid, monocrotaline, causes pulmonary microvascular thrombosis that is associated with vascular remodeling and pulmonary hypertension. It is possible that vascular thrombi contribute to the lesions that occur after MCTP treatment. Since MCTP is toxic to pulmonary endothelial cells and because the pulmonary endothelium is in a unique position to influence procoagulant and fibrinolytic reactions in the lungs, we examined changes in the procoagulant and fibrinolytic properties of cultured pulmonary artery endothelial cells exposed to MCTP to see if they might favor thrombosis. Monolayers of confluent bovine pulmonary arterial endothelial cells received a single administration of MCTP or N,N-dimethylformamide vehicle, and the media or lysates were examined at 4, 24, 48, or 120 hr after treatment. MCTP caused a time-dependent cell detachment and an increase in release of lactate dehydrogenase into culture medium. Although cell numbers decreased dramatically with time, the protein concentration of cell monolayer lysates was unchanged by treatment. MCTP treatment caused no change in the amount of tissue factor activity/micrograms cellular protein in bovine endothelial cell lysates and only a small increase in the activity of Factor V in the culture medium at 120 hr. In addition, the medium from bovine endothelial cells treated with MCTP had a time-dependent increase in the activity of plasminogen activators and a decrease in the activity of plasminogen activator inhibitors. Thus bovine endothelial cells exposed to MCTP in vitro do not produce changes in these procoagulant or fibrinolytic properties that would explain the thrombosis observed in vivo.
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PMID:Procoagulant and fibrinolytic properties of bovine endothelial cells treated with monocrotaline pyrrole. 837 34

To evaluate the toxicity of cadmium on the blood fibrinolytic system during hemostasis, human vascular smooth muscle cells and human fibroblasts were cultured in the presence of cadmium chloride. It was found that cadmium markedly decreased the release of both tissue plasminogen activator antigen (t-PA:Ag) and plasminogen activator inhibitor type-1 antigen (PAI-1:Ag) from vascular smooth muscle cells. Other heavy metals including lead, manganese, mercury and nickel also decreased the t-PA:Ag and PAI-1:Ag release, however, cadmium was the most potent inhibitor. On the other hand, the release of t-PA:Ag was significantly increased whereas that of PAI-1:Ag was unaffected in fibroblasts after exposure to cadmium. Of the tested heavy metals, only cadmium increased the t-PA:Ag release from the cells. Electrophoretic enzymography revealed that cadmium reduced the activity of plasminogen activators in the conditioned medium of both vascular smooth muscle cells and fibroblasts. Cadmium markedly decreased the incorporation of [3H]leucine accompanied with a significant increase in the leakage of lactate dehydrogenase in vascular smooth muscle cells; however, the metal did not change these markers in fibroblasts. These results suggest that the regulation of fibrinolysis mediated by vascular smooth muscle cells and fibroblasts during hemostasis may be disturbed by cadmium.
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PMID:Effects of cadmium on the release of tissue plasminogen activator and plasminogen activator inhibitor type 1 from cultured human vascular smooth muscle cells and fibroblasts. 857 89

Cytotoxicity indicated by increased release of prelabeled 51chromium (51Cr) and lactate dehydrogenase (LDH) was studied in human prostate cancer and melanoma cells in cell culture following irradiation or exposure to several injurious substances. These changes were compared to those observed in bovine aortic endothelial cells (BAEC) subjected to identical treatments. Further, the effect of irradiation on plasminogen activator (PA) secretion from prostate cancer cells, and the effect of glycine on radiation-induced cytotoxicity in BAEC were also investigated. Radiation, lipopolysaccharide and xanthine/xanthine oxidase stimulated no release of 51Cr or LDH from tumor cells, while these treatments induced a dose- and time-related loss of those cytotoxic indicators from BAEC. Protease, elastase and Triton X-100 incited loss of 51Cr and LDH from all three cell types. Radiation, lipopolysaccharide and xanthine/xanthine oxidase have been shown to cause cell injury via a common pathogenic pathway of oxidant generation. Tumor cells appear quite resistant to oxidant stress. Cell damage precipitated by protease, elastase and Triton probably involves hydrolysis of proteins and phospholipids in the cell membrane, leading to an increased leakage of intracellular proteins such as LDH and those bound with 51Cr. Radiation caused a dose- and time-related reduction in the secretion of PA from prostate cancer cells. PA is alleged to play a role in tumor metastasis; the reduced secretion could be another beneficial effect of radiation, in addition to interruption of cell proliferation, in the impediment of tumor growth and spread. Glycine diminished cytotoxic injury of BAEC inflicted by radiation. This amino acid may prove useful in offering a degree of protection of normal tissue against radiation associated side-effects.
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PMID:Injury-specific cytotoxic response of tumor cells and endothelial cells. 868 34

To evaluate the toxicity of lead on the blood fibrinolytic system during hemostasis, human aortic smooth muscle cells and human fetal lung fibroblasts were cultured in the presence of lead chloride. Tissue plasminogen activator antigen (t-PA:Ag) and plasminogen activator inhibitor-1 antigen (PAI-1:Ag) released were determined by enzyme immunoassay. It was found that lead decreased the release of both t-PA:Ag and PAI-1:Ag from vascular smooth muscle cells. On the other hand, in fibroblasts, the release of t-PA:Ag was markedly decreased whereas that of PAI-1:Ag was markedly increased by the metal. Fibrin zymography showed that lead reduced the plasminogen activator activity in the conditioned medium of both cell types. However, lead did not cause a nonspecific cell damage and an alteration of protein synthesis when evaluated by lactate dehydrogenase leakage and [14C]leucine incorporation, respectively. Lead accumulated within either vascular smooth muscle cells or fibroblasts in a dose-dependent manner; intracellular accumulation of calcium could be increased by lead. However, the effects of lead on the release of t-PA:Ag and PAI-1:Ag were different from those of calcium ionophore A23187. It was therefore suggested that regulation of spontaneous release of fibrinolytic proteins from subendothelial cells is disturbed by lead through intracellular calcium-independent pathway.
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PMID:Lead perturbs the regulation of spontaneous release of tissue plasminogen activator and plasminogen activator inhibitor-1 from vascular smooth muscle cells and fibroblasts in culture. 905 94

The lung plasminogen activator (PA) response was examined in four different models of particle-induced pulmonary lesions in NMRI mice (single intratracheal administration, 0.75 to 5 mg/mouse). Sequential changes in cellular (total and differential counts) and biochemical markers of alveolitis (lactate dehydrogenase [LDH], total proteins) were monitored in bronchoalveolar fluid (BALF) and the fibrotic lung response was assessed histologically. An intense but spontaneously resolving alveolitis was produced by manganese dioxide (MnO2) and a fibrosing alveolitis was elicited by crystalline silica (DQ12). Minimal and noninflammatory responses were obtained after instillation of titanium dioxide (TiO2) and tungsten carbide (WC), respectively. The comparison between the resolving and the fibrosing alveolitis model was especially taken into consideration in an attempt to identify fibrinolytic changes associated with the development of fibrosis. At the alveolitis stage, similarly increased BALF PA activities were measured in both the resolving and the fibrosing alveolitis models whereas only slight and no PA modifications were noted after administration of TiO2 and WC, respectively. Persistently (up to 120 d) increased BALF PA activity was selectively associated with the progression to fibrosis (DQ12), suggesting that PA is involved in the fibrotic process. ELISA measurements demonstrated that the changes in BALF PA activity were exclusively related to changes in urokinase (uPA), not tissue-type PA. A rapid and persisting (up to Day 30) upregulation of cell-associated PA activity occurred after DQ12, MnO2, and TiO2 treatment only. Cellular PA activity was however significantly higher in fibrogenic inflammatory cells recovered from DQ12 than from MnO2-treated mice suggesting that the intensity of cellular PA upregulation may represent an early indicator of the progression to fibrosis. The implication of urokinase in the pathogenesis of silica-induced fibrosis was demonstrated by the use of a uPA knockout mice. The acceleration of the fibrotic process in uPA-deficient compared with the wild type animals demonstrated the contribution of uPA to limit the fibrotic process.
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PMID:Role of urokinase in the fibrogenic response of the lung to mineral particles. 947 81

Previously we reported that 1-methyl-4-phenylpyridinium ion (MPP(+)), a dopaminergic neurotoxin, induced apoptosis of GH3 cells established from rat anterior pituitary. In the present study, the role of MPP(+) along with that of other apoptotic factors such as Ca(2+) and H(2)O(2) in cell death was examined. Ionomycin induced DNA fragmentation and lactate dehydrogenase (LDH) leakage in GH3 cells. H(2)O(2) also induced LDH leakage. Co-addition of MPP(+), in conditions where MPP(+) had no effect by itself, enhanced ionomycin- and H(2)O(2)-induced cell death. Because the stimulation of phospholipase A(2) (PLA(2)) causing arachidonic acid (AA) release has been proposed to be involved in neuronal cell death, the effect of MPP(+) on AA release in GH3 cells was investigated. MPP(+) treatment for 8 h enhanced ionomycin- and H(2)O(2)-stimulated AA release mediated by activation of cytosolic PLA(2) in a concentration-dependent manner, although MPP(+) by itself had no effect on AA release. An inhibitor of cytosolic PLA(2) inhibited MPP(+)-induced cell death. These findings suggest a synergistic effect of MPP(+) on Ca(2+)- and H(2)O(2)-induced cell death, and the involvement of cytosolic PLA(2) activation in MPP(+)-induced cell death in GH3 cells. Pretreatment with a caspase inhibitor or EGF did not modify the ionomycin- or H(2)O(2)-induced AA release, or enhancement by MPP(+), but the pretreatment inhibited the cell death in the presence and absence of MPP(+). The involvement of caspase(s) on activation of PLA(2) by MPP(+) was excluded, and EGF inhibited MPP(+)-induced cell death downstream of the AA release.
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PMID:Possible involvement of cytosolic phospholipase A(2) in cell death induced by 1-methyl-4-phenylpyridinium ion, a dopaminergic neurotoxin, in GH3 cells. 1067 96


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