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)

Leukocytes can generate a substance that, when added to some partially purified human kininogen, is capable of forming kinins. The addition of endotoxin or polystyrene latex particles to the incubated leukocytes doubled the amount of kinin generated. Certain preparations of kininogen, however, failed to allow kinin formation by the leukocytes. No evidence could be found that an activator of prekallikrein or a kallikrein was present in the granulocyte preparations. However, the addition of highly purified plasminogen to inactive kininogen preparations restored their ability to generate kinins in the presence of leukocytes. All the kininogen preparations that allowed kinin formation when incubated with leukocytes contained plasminogen. These data suggest that a plasminogen activator is present on the leukocyte surface. This activator activates plasminogen to form plasmin which in turn acts on kininogen to release a kinin and thus provides a mechanism for the formation of kinins in inflammatory exudates and during endotoxemia.
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PMID:Interaction of leukocytes and endotoxin with the plasmin and kinin systems. 12 70

The negative surface charge of human granulocytes was diminished after incubation with the chemotactic factors C5a, dialyzable transfer factor, and the enzymes kallikrein and plasminogen activator. No such change was observed after incubation with human IgG, albumin, horeseradish peroxidase, or a mixture of prekallikrein and plaminogen proactivator. Hydrocortisone inhibited the effect of C5a upon granulocyte surface charge and inhibited its chemotactic activity, suggesting that steroids act at the cell surface. The chemotactic inhibitors cholchicine and cytochalsin B had no effect upon granulocyte surface charge, consistent with their presumed effect upon microtubules and microfilaments, respectively. The data suggest that the decrease in cell surface charge may be a preerequiste for normal cell movement.
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PMID:Interaction of leukocyte chemotactic factors with the cell surface. I. Chemotactic factor-induced changes in human granulocyte surface charge. 112 32

Endotoxemia in patients can lead to sepsis and shock by activation of cellular and plasmatic systems. Corticosteroids are described to have a beneficial effect on these phenomena. In this study of controlled endotoxic shock, we investigated the protective effects of prophylactic corticosteroid treatment against activation of cellular and plasmatic systems. In this respect, a low-dose methylprednisolone (1 mg/kg body wt) treatment was compared with that of a high-dose methylprednisolone (40 mg/kg body wt) treatment. Endotoxin infusion induced death of all rabbits, which was associated with leukopenia, thrombopenia, increased levels of beta-glucuronidase, and leukotriene B4 (LTB4) and decreased levels of complement total hemolytic activity (CH50) and tissue plasminogen activator (t-PA) activity. Both methylprednisolone regimens prevented death of the rabbits after endotoxin infusion, which correlated with a significant decrease of the granulocyte release product beta-glucuronidase (P less than 0.01). The early leukopenia and thrombopenia were not prevented; however, both cell numbers returned more rapidly to baseline values than in the placebo group (P less than 0.01, P less than 0.05). The LTB4 and CH50 concentration and t-PA activity did not differ significantly between the treated and placebo groups. These results indicate that although methylprednisolone has no inhibitory effect on the activation of the complement, arachidonic acid, and fibrinolytic systems, it protected the animals from the deleterious effects of endotoxin shock by inhibition of leukocyte activation. In this regard a low dosage of methylprednisolone is equally effective as the most often recommended high dose.
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PMID:Methylprednisolone prophylaxis protects against endotoxin-induced death in rabbits. 164 35

The plasminogen activator (PA)/plasmin system has been implicated in the inflammation and connective tissue remodelling occurring in arthritic joints. PA activity is detected in cultures of human monocytes, synoviocytes and chondrocytes and can be regulated by a variety of cytokines found in diseased joints; PA inhibitors (PAI-1 and/or PAI-2) are also produced by these cells. We have shown that human monocytes can synthesize both urokinase-type PA (u-PA) and tissue-type PA (t-PA). One cytokine present in rheumatoid synovial fluids, granulocyte macrophage colony stimulating factor (GM-CSF), stimulates monocyte u-PA production; since this cytokine can also be produced by activated monocytes and other cell types in joints, than a "CSF network" can be produced leading to u-PA production. Another monocyte cytokine, interleukin 1, causes human synoviocytes to increase their u-PA expression, a response which can be dependent on the presence of endogenous cyclooxygenase products; this cytokine also causes human chondrocytes and cartilage tissue to produce increased u-PA and t-PA activity, i.e., under conditions during which cartilage is resorbed.
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PMID:Regulation of plasminogen activator activity in arthritic joints. 190 74

Clinical trials of recombinant biologic agents have resulted in new treatment options for hematologic, oncologic, and cardiologic disorders. These agents include the interferons, recombinant human erythropoietin (r-HuEPO), colony-stimulating factors (CSFs), interleukins (ILs), and tissue plasminogen activator (t-PA). Interferon alfa has proven efficacious in treating certain hematologic malignancies and solid tumors and has recently been indicated for acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma. Treatment with r-HuEPO has relieved the chronic anemia of hemodialysis patients. Recombinant human granulocyte CSF (G-CSF) or human granulocyte macrophage CSF (GM-CSF) has been used to treat patients after autologous bone marrow transplantation for lymphoid or solid malignancies, resulting in increased production of granulocytes and platelets. G-CSF and GM-CSF have been used to treat aplastic anemia, myelodysplastic syndromes, chemotherapy-induced neutropenia, and neutropenia associated with AIDS. In patients with evolving myocardial infarction, the recombinant agent t-PA has proved more efficacious than streptokinase in terms of average coronary artery patency rates and survival rates in patients with evolving myocardial infarction. While these agents all offer promising therapeutic advances, the expenses associated with developing and testing biotherapeutic substances have resulted in high treatment costs. Since in many instances investigational therapy is the best treatment option available, physicians, patients, the pharmaceutical industry, the government, and insurance carriers must work together to ensure that these therapies are financially available to those in need.
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PMID:New directions in hematologic biotherapy. 247 3

Previous studies have shown that the response of patients with acute myeloid leukemia to induction chemotherapy can be predicted by the species of plasminogen activator that their cells secrete. Patients whose cells secreted tissue plasminogen activator (tPA) only failed to respond to combination chemotherapy. Individuals whose leukemic cells display features of the early progenitor phenotype also respond poorly to therapy. This suggested that the two species of plasminogen activator secreted by leukemic cells might be produced by normal cells at distinct stages of differentiation. These results indicate that the secretion of the two enzyme types is a differentiation-linked property of normal cells with tPA being produced by granulocyte/macrophage progenitors and urokinase by more differentiated cells and by mature neutrophils and macrophages.
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PMID:Differentiation-linked secretion of urokinase and tissue plasminogen activator by normal human hemopoietic cells. 310 48

Preparative isoelectrofocusing used for fractionating the whole human granulocyte lysate serine proteinases revealed multiple forms of elastase, cathepsin G, kininogenase, human granulocytes plasminogen activator (pI 6.2-10.75). Kinetic characteristics of their substrate specificity were also obtained. It is shown that serine kininogenase of human granulocytes is not identical with elastase as it had been supposed before, it is of trypsin-like nature and is identical with plasminogen activator of these cells. The results obtained reveal new aspects in comprehension of the role of the granulocyte plasminogen activator in development of the inflammatory reaction. It is found that acid-stable proteinase inhibitors formed from blood plasma inter-alpha-inhibitor of trypsin, have an inhibitory effect on the granulocyte plasminogen activator, that supports an assumption on the anti-inflammatory function of these inhibitors.
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PMID:[Identity of human granulocyte kininogenase and plasminogen activator]. 634 22

It was shown that the plasminogen activator inhibitor, ZGlyGlyArgCH2Cl, inactivates the kininogenase and plasminogen activator activities in the whole human granulocyte lysate and human granulocyte proteinase fractions isolated by isoelectrofocusing from the granulocyte lysate (pH 3-10). The kinetics of irreversible inhibition of the ZGlyGlyArgpNA-amidase activity in granulocyte proteinase fractions (pI 10.75, 8.9 and 8.3) by ZGlyGlyArgCH2Cl was measured. These data confirm the earlier obtained results on the trypsin-like nature of the human granulocyte plasminogen activator and its identity to this cell kininogenase.
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PMID:[Identity of kininogenase and plasminogen activators in human granulocytes]. 642 31

Expression of the receptor for the urokinase type plasminogen activator (uPAR) has been studied by flow cytometry and immunohistology in normal blood and bone marrow cells, in vitro activated lymphoid cells, and tissue samples from reactive lymph nodes (n = 6), thymus (n = 2) and malignant lymphomas (n = 82), or leukemias (n = 32). HL-60 myeloid precursor cells and CD34-positive normal stem cells also were analyzed. In the normal cells, staining was confined to monocytes, macrophages, neutrophils, and myeloid precursors. No labelling was seen of normal or activated lymphoid cells. Purified CD34-positive hematopoietic progenitors were uPAR negative, but expressed uPAR during differentiation in short-term liquid culture stimulated in vitro by recombinant interleukin (IL)-1, IL-3, IL-6, granulocyte-macrophage colony stimulating factor (CSF), granulocyte-CSF, and stem cell factor. Enhanced uPAR expression was also seen in HL-60 cells after induction of differentiation with dimethyl sulfoxide or 1 alpha,25-dihydroxyvitamin D3. In lymphomas and leukemias, the staining pattern was similar to that seen in the normal cells with labelling of monocytic and myeloid that seen in the normal cells with labelling of monocytic and myeloid malignancies, but not of the neoplastic cells in B-cell or T-cell lymphomas or Hodgkin's disease. In conclusion, uPAR is a differentiation marker for myeloid and monocytic cells, and may act to facilitate migration of these cells in normal and pathologic conditions by cell-associated plasminogen activation. Whether expression of uPAR in myeloid and monocytic malignancies relates to their growth and behavior will be an important topic for investigations in the future.
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PMID:Expression of the receptor for urokinase-type plasminogen activator in normal and neoplastic blood cells and hematopoietic tissue. 780 1

The neutrophil granulocyte seems to be intimately involved in the destructive processes leading to myocardial damage observed in ischaemic/reperfusion injuries. The process may cause stress to the peripheral circulating neutrophils leading to exhaustion and decreased function. We conducted a study in which the function of peripheral neutrophil granulocytes was measured in 21 patients with an acute myocardial infarction 0-24 and 48-72 h after the onset of symptoms. Ten patients received thrombolytic treatment (streptokinase). Neutrophil function was judged by superoxide generating capacity and chemotactic ability. Compared to healthy controls neutrophil function was found to be preserved in patients with myocardial infarction. Furthermore, streptokinase treatment of the patients did not modulate neutrophil function. In-vitro studies demonstrated that low concentrations of streptokinase (12-300 U.ml-1) or recombinant plasminogen activator (0.12 micrograms.ml(-1)-3.0 micrograms.ml-1) did not influence neutrophil superoxide generation. However, at higher concentrations (100-10,000 U.ml-1 and 10-100 micrograms.ml-1 respectively) both thrombolytics induced a significant increase in phorbol myristate acetate-stimulated superoxide generation. Neither of the thrombolytics influenced neutrophil chemotaxis in vitro. It is concluded that neither myocardial infarction nor streptokinase treatment decrease superoxide generating capacity or chemotactic ability of circulating neutrophils.
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PMID:Preserved oxidative activity and chemotaxis of circulating neutrophils in patients with acute myocardial infarction. 839 84


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