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)

The effects of activation of plasminogen by streptokinase and tissue-type-plasminogen activator on platelet activation and the membrane glycoproteins (GPs) that mediate platelet adhesion and aggregation are not yet fully defined. To clarify effects on platelets during activation of plasminogen in vitro, we used monoclonal antibodies (MoAbs), flow cytometry, and platelets surface-labeled with 125I to characterize changes in receptors for fibrinogen (GPIIb-IIIa), von Willebrand factor (GPIb), and collagen (GPIa-IIa). Activation of plasminogen in plasma with pharmacologic concentrations of plasminogen activators did not degrade GPIIb-IIIa or GPIb, and caused only a modest decrease in GPIa. In washed platelets GPIIb-IIIa was extensively degraded by plasmin at 37 degrees C in the absence of exogenous Ca2+, conditions that destabilize the IIb-IIIa complex. Degradation of GPIb in washed platelets displayed a similar although less-marked dependence on temperature and the absence of Ca2+. The binding of activation-specific MoAbs did not increase during activation of plasminogen in plasma. We conclude that during pharmacologic fibrinolysis, reported inhibition of platelet function in plasma is not due to degradation of platelet-adhesive receptors. In addition, platelet activation observed during thrombolytic therapy does not appear to be a direct consequence of plasminogen activation.
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PMID:Dependence of plasmin-mediated degradation of platelet adhesive receptors on temperature and Ca2+. 216 24

Commercial aurintricarboxylic acid (ATA) was separated into molecular-weight (MW) fractions of < 210 to > 25,000, using gel permeation chromatography. Fractions with MW > 1,300 effectively inhibited both botrocetin-induced vWF and bovine vWF binding to fixed human platelets. These activities decreased with a MW > 17,000. Platelet retention for a human in vitro was reduced by ATA at 150 microM, as was that for rats ex vivo at 3 mg/kg. ATA prolonged tail transection bleeding time in rats but had only a weak effect on buccal mucosal bleeding time in dogs. ATA had no effect on platelet count but markedly prolonged PTT. ATA at 10 mg/kg exhibited antithrombotic activity and caused a marked improvement in patency status following successful thrombolysis by t-PA in electrically and copper coil-induced thrombosis models. These results suggest that specific inhibitors of the vWF-GPIb interaction such as ATA may prove useful as antithrombotic agents.
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PMID:Inhibition by aurintricarboxylic acid of von Willebrand factor binding to platelet GPIb, platelet retention, and thrombus formation in vivo. 804 18

This study was undertaken to determine the role of platelet glycoprotein (GP) IIb/IIIa receptors in the modulation of plasminogen activator type-1 (PAI-1) release from human platelets as compared to other platelet functions. To address this issue, the effect of various agonists on human platelet aggregation, [125I]fibrinogen binding and the release of PAI-1 was examined in normal and Glanzmann's thrombasthenic (GT) platelets. In control subjects, maximum platelet aggregation and PAI-1 secretion were observed within 5 min in response to the different agonists including thrombin, collagen, adenosine diphosphate (ADP), and arachidonic acid. Agonist-induced platelet GpIIb/IIIa receptor activation was confirmed by [125I]fibrinogen binding analysis. In contrast, platelets from GT subjects demonstrated a lack of fibrinogen binding and a lack of an aggregatory response to all agonists tested except to the GPIb- mediated aggregation induced by ristocetin. However, GT platelets demonstrated normal responsiveness in secreting PAI-1 in response to the various agonists. Similarly, when platelet GpIIb/IIIa receptors were blocked in normal platelets by the tripeptide Arg-Gly-Asp (RGD) or the tetrapeptide Arg-Gly-Asp-Ser (RGDS) at 10(-3) M, agonist-induced platelet aggregation and fibrinogen binding were blocked, but platelet PAI-1 release was not blocked. Furthermore, flow cytometric analysis using dual fluorescence markers for the platelet GPIIb/IIIa membrane receptors (FITC-labeled cyclic RGD analog, XL086) and for the alpha granule (PE-monoclonal antibody for P-selectin) demonstrated a dissociation between the platelet GPIIb/IIIa receptors and granular secretion. These results suggest a lack of a role for platelet GpIIb/IIIa receptors in the modulation of platelet PAI-1 release.
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PMID:Role of platelet GpIIb/IIIa receptors in the modulation of platelet plasminogen activator inhibitors type-1 (PAI-1) release. 815 39

Platelet transfusion therapy became to be largely used in the last 20 years. This development was related to the progress of plastic bags and of blood cell separators. In parallel the platelet immunology has moved from serological techniques to molecular biology. The biochemical characterization of platelet antigen and the genetic basis of the polymorphism was discovered in the last years. The platelet RNA PCR amplification and specific oligonucleotide typing are now accessible to several laboratories. Five major human platelet antigen (HPA) systems are completely characterized. HPA-1 (PLA, Zw) localized on platelet glycoprotein GPIIIa correspond to a single amino acid substitution (leu<==> Pro 33). HPA-2 (Ko, Sib) present on GPIb is due to a Thre<==>Met substitution in 145. HPA-3 formerly Bak, Lek correspond to a polymorphism in 843 (Ile<==>ser) on GPIIb. HPA-4 (Pen, Yuk) as HPA1 is on GPIIIa but in a different location (Arg<==>Gln 143). HPA-5 (Br, He, Zav) and HPA-6 (Ca, Tu) are on GPIa and GPIIIa respectively. The major progress made in the field of platelet immunology has not yet been largely applied to the clinical situation of platelet transfusion. We can hope that it could help in the future to a better platelet-transfusion compatibility and consequently an improved clinical efficacy of platelet transfusion.
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PMID:Platelet alloantigens and transfusion. 833 18

Heparin-induced thrombocytopenia (HIT), a well recognized complication of heparin administration, is associated with thrombotic complications. An immunologic mechanism is believed to be responsible for the thrombocytopenia, but the cause of thrombosis is not fully understood. We report a histological and immunohistochemical study of thrombosed vessels in surgically removed ischemic tissues in patients with HIT complicated by gangrene of the lower limbs. Tissue sections were studied by: (1) hematoxylin and eosin staining and immunoperoxidase staining using a monoclonal antibody against platelet surface glycoprotein Ib(GPIb) for the identification of platelets, and (2) polyclonal antibodies against tissue-type plasminogen activator (tPA) and factor VIII for the identification of endothelial cells. We observed small arteries occluded by multiple small platelet thrombi surrounded by proliferative endothelial cells. In addition, depositions of IgG, IgA, and IgM were found in the occluded arteries. We postulate that the endothelial cell hyperplasia is caused by immunologic injury to endothelial cells as a result of immunoglobulin deposition, and by various mitogens derived from the activated platelets in the thrombi. Such endothelial cell hyperplasia is a major contributory factor, in addition to the microthrombi, of the occlusive vasculature in this disease.
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PMID:Endothelial cell hyperplasia contributes to thrombosis in heparin-induced thrombocytopenia. 1035 48

The interaction of fibrinolytic components with GPIb/V/IX of platelets on thrombus formation, was investigated in mice deficient in tissue type (tPA-/-), urokinase type plasminogen activator (uPA-/-) or plasminogen activator inhibitor-1 (PAI-1-/-) and in their wild type control (tPA+/+, uPA+/+, PAI-1+/+). A thrombus was induced in the murine carotid artery using a photochemical reaction. The times to occlusion after the initiation of endothelial injury in all wild type mice was within 12 min, and no significant changes in occlusion delay were observed in uPA-/- and tPA-/- mice compared to wild type mice, whereas that of PAI-1 mice were significantly prolonged (16.9+/-2.9 min, P<0.05). When high molecular weight aurintricarboxylic acid (ATA), an inhibitor of platelet glycoprotein Ib/V/IX, was administered, the time to occlusion was prolonged in a dose-dependent manner in all types of mice. However, when this compound was injected in tPA-/- mice, the most significant changes were observed: i.e. the estimated ED(50) was 20.2 times higher than that in tPA+/+ mice, but the estimated ED(50) in uPA-/- mice was not changed as compared with that of wild type mice. On the other hand, when ATA was injected in PAI-1-/- mice, the estimated ED(50) was significantly decreased (P<0.05). Platelet aggregation induced by botrocetin was not significantly different among all types of mice. The bleeding time was prolonged in a dose dependent-manner when ATA was injected in all types of mice. In conclusion, the antithrombotic effect of inhibition of platelet GPIb/V/IX is severely affected by the absence or presence of tPA-production on thrombus formation and the inhibition of PAI-1 could enhance this antithrombotic effect.
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PMID:The interaction between components of the fibrinolytic system and GPIb/V/IX of platelets thrombus formation in mice. 1103 Jul 38