Fibrinolysis and Proteolysis最新文献

{"title":"Glycosylation dependent conformational transitions in plasminogen activator inhibitor-1: evidence for the presence of two active conformations","authors":"A. Gils, I. Knockaert, E. Brouwers, P.J. Declerck","doi":"10.1054/fipr.2000.0062","DOIUrl":"https://doi.org/10.1054/fipr.2000.0062","url":null,"abstract":"Abstract Plasminogen activator inhibitor-1 (PAI-1) is a unique member of the serpin superfamily because of its conformational and functional flexibility. Different systems have been used to express PAI-1, e.g. Chinese hamster overy (CHO) cells, Escherichia coli cells and HT 1080 cells. Although glycosylation may influence the biochemical properties of proteins, to date minor differences have been observed between glycosylated and non-glycosylated PAI-1. In the present study, we have investigated the effect of glycosylation on the inactivation of PAI-1 by Triton X-100 and the associated pathways of conformational transitions. Whereas in the absence of Triton X-100, the observed PAI-1 stability was independent on the source of PAI-1, the addition of Triton X-100 revealed major glycosylation-dependent differences in the inactivation process of PAI-1. Incubation at 0°C in the presence of Triton X-100 resulted in a conversion of the active conformation to a substrate-like conformation for all PAI-1 molecules examined. The rate (k) of this conversion was 0.00016 s –1 and 0.00121 s –1 for non-glycosylated PAI-1 and CHO-PAI-1, respectively. When incubating non-glycosylated PAI-1 with 0.2% Triton X-100 at 37°C, two consecutive conformational transitions occur ultimately resulting in a complete conversion to the latent conformation. However, incubation of recombinant CHO-PAI-1 under these conditions yielded significantly different pathways of conformational transitions, i.e. a rapid conversion (k 1 >0.035 s –1 ) of part (39%) of the active conformation into a stable substrate conformation and a slower conversion (k 1 =0.0004 s –1 ) of the remaining part (61%) of the active conformation into the latent conformation, revealing the existence of two distinct active conformations. In conclusion, this is the first report describing significant differences between glycosylated and non-glycosylated PAI-1. Both the rate and the pathways of induced conformational transitions and concomitant inactivation of PAI-1 depend strongly on the glycosylation.","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"14 1","pages":"58-64"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71794372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author index to Volume 13","authors":"","doi":"10.1054/fipr.2000.0050","DOIUrl":"https://doi.org/10.1054/fipr.2000.0050","url":null,"abstract":"","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"13 6","pages":"Pages 282-283"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71824204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PAI-2 inhibits the chemiluminescence of phagocytes and suppresses autoimmunity","authors":"T. Stief, H. Schorlemmer, I. Beck-Speier, M. Doss","doi":"10.1054/FIPR.1999.0038","DOIUrl":"https://doi.org/10.1054/FIPR.1999.0038","url":null,"abstract":"Abstract Activated phagocytes participate in inflammation and in the lysis of tissue or fibrin. An important inflammation mediator is singlet molecular oxygen ( 1 O 2 ), an excited oxidant that emits light when it reverts to its ground state. Other products of activated macrophages are urokinase (u-PA) and plasminogen activator inhibitor (PAI)-2. PAI-2 in physiological concentrations inhibited the hydrogen peroxide-dependent chemiluminescence (CL) of human phagocytes: 1 unit/ml (about 10 ng/ml) of PAI-2 decreased the CL of 2 × 10 5 neutrophil granulocytes to about 50%. Preincubation of PAI-2 with excess amounts of urokinase, resulting in complexed PAI-2, also decreased CL. 5 units of PAI-2 injected intraperitoneally in mice suppressed, 2 or 24 h post injection, the CL of stimulated peritoneal macrophages by 48 or 67% respectively. Rats with experimental allergic encephalomyelitis (EAE), an animal model for the human disorder multiple sclerosis (MS), were treated with PAI-2. The inhibitor was injected intraperitoneally (1) at days 0–9 or (2) at days 7–16 after EAE induction. At 17.4 ± 1.5 days after EAE induction, non-treated control rats died. In contrast, 40 out of 40 animals treated with ≥50 units of PAI-2/ animal/ day survived. Treatment with 100 units of PAI-2/ animal/day resulted in less paralytic complications, especially when PAI-2 was injected at days 7–16 after EAE induction. Women with MS have a decreased disease intensity in pregnancy. PAI-2 is elevated in blood of healthy pregnant women (about 30 units/ml PAI-2 at term). Imitation of this physiologic immunsuppression by therapeutic application of PAI-2 could be indicated in a broad range of human diseases of autoimmune character, such as MS. The present findings could have relevance for the understanding of the pathogenesis of autoimmunity.","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"243 1","pages":"245-251"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75054726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local and systemic changes of fibrinolytic parameters in blood during catheter-directed intra-arterial thrombolysis","authors":"M. Kozak,&nbsp;D. Keber,&nbsp;M. Sabovic","doi":"10.1054/fipr.2000.0039","DOIUrl":"https://doi.org/10.1054/fipr.2000.0039","url":null,"abstract":"<div><p>Fibrinolytic parameters (plasminogen, fibrinogen, alpha2-antiplasmin, euglobulin clot lysis time and D-dimers) were measured locally near the occlusive peripheral arterial thrombus and in systemic blood of 27 patients treated by catheter-directed thrombolysis with streptokinase. The parameters were measured simultaneously in systemic (venous) and in local (arterial) blood before and 0.5, 1.5, 4, 8, 24 and 48 h after the start of treatment with streptokinase (3750 IU/h). A time-dependent decrease in the concentrations of plasminogen, alpha2-antiplasmin and fibrinogen was measured in both arterial and venous blood, reaching: for plasminogen 39 and 47, for alpha2-antiplasmin 18 and 26, and for fibrinogen 50% and 61%, respectively, of the pretreatment values. A time-dependent increase in D-dimer levels and a shortening of euglobulin clot lysis time were also detected. The differences between time-related arterial and venous samples were significant at least for the first 24 h and became smaller after 48 h of treatment, when at least partial recanalization was achieved in the majority of patients. Our results show that the concentration of plasminogen is significantly reduced during catheter-directed thrombolysis in the systemic blood and even more in the blood surrounding the thrombus. This might reduce the efficacy of intra-arterial catheter-directed thrombolysis.</p></div>","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"13 6","pages":"Pages 259-263"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71824199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of cancer invasion and vascularization by plasminogen activator inhibitor-1","authors":"A. Noël ,&nbsp;K. Bajou ,&nbsp;V. Masson ,&nbsp;L. Devy ,&nbsp;F. Frankenne ,&nbsp;J.M. Rakic ,&nbsp;V. Lambert ,&nbsp;P. Carmeliet ,&nbsp;J.M. Foidart","doi":"10.1054/fipr.2000.0043","DOIUrl":"https://doi.org/10.1054/fipr.2000.0043","url":null,"abstract":"<div><p>Acquisition of invasive/metastatic potential through protease expression is a key event in tumor progression. The proteolytic enzyme plasmin is generated from the precursor plasminogen by the action of urokinase-type plasminogen activator (urokinase, uPA) or tissue-type plasminogen activator (tPA). Plasminogen activator inhibitor-1 or PAI-1 is the main inhibitor of uPA and tPA. High levels of components of this proteolytic system, including uPA and its cell surface receptor (uPAR), have been correlated with a poor prognosis for different cancers. It was therefore anticipated that PAI-1 expression would be associated with favorable outcome. Paradoxically, high rather than low PAI-1 levels predict poor survival of patients suffering from a variety of cancers. Recent observations indicate a much more complex role of PAI-1 in tumor progression and angiogenesis than initially expected. The exact mechanisms of this multifunctional molecule remain puzzling.</p></div>","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"13 6","pages":"Pages 220-225"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71824424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PAI-2 inhibits the chemiluminescence of phagocytes and suppresses autoimmunity","authors":"T.W. Stief ,&nbsp;H.U. Schorlemmer ,&nbsp;I. Beck-Speier ,&nbsp;M.O. Doss","doi":"10.1054/fipr.1999.0038","DOIUrl":"https://doi.org/10.1054/fipr.1999.0038","url":null,"abstract":"<div><p>Activated phagocytes participate in inflammation and in the lysis of tissue or fibrin. An important inflammation mediator is singlet molecular oxygen (¹O₂), an excited oxidant that emits light when it reverts to its ground state. Other products of activated macrophages are urokinase (u-PA) and plasminogen activator inhibitor (PAI)-2. PAI-2 in physiological concentrations inhibited the hydrogen peroxide-dependent chemiluminescence (CL) of human phagocytes: 1 unit/ml (about 10 ng/ml) of PAI-2 decreased the CL of 2 × 10⁵neutrophil granulocytes to about 50%. Preincubation of PAI-2 with excess amounts of urokinase, resulting in complexed PAI-2, also decreased CL. 5 units of PAI-2 injected intraperitoneally in mice suppressed, 2 or 24 h post injection, the CL of stimulated peritoneal macrophages by 48 or 67% respectively. Rats with experimental allergic encephalomyelitis (EAE), an animal model for the human disorder multiple sclerosis (MS), were treated with PAI-2. The inhibitor was injected intraperitoneally (1) at days 0–9 or (2) at days 7–16 after EAE induction. At 17.4 ± 1.5 days after EAE induction, non-treated control rats died. In contrast, 40 out of 40 animals treated with ≥50 units of PAI-2/ animal/ day survived. Treatment with 100 units of PAI-2/ animal/day resulted in less paralytic complications, especially when PAI-2 was injected at days 7–16 after EAE induction. Women with MS have a decreased disease intensity in pregnancy. PAI-2 is elevated in blood of healthy pregnant women (about 30 units/ml PAI-2 at term). Imitation of this physiologic immunsuppression by therapeutic application of PAI-2 could be indicated in a broad range of human diseases of autoimmune character, such as MS. The present findings could have relevance for the understanding of the pathogenesis of autoimmunity.</p></div>","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"13 6","pages":"Pages 245-251"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.1999.0038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71824431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral contraceptive use is associated with a systemic acute phase response","authors":"M. Fröhlich, A. Döring, A. Imhof, W. Hutchinson, M. Pepys, W. Koenig","doi":"10.1054/FIPR.1999.0037","DOIUrl":"https://doi.org/10.1054/FIPR.1999.0037","url":null,"abstract":"Objective: We determined whether reported intake of oral contraceptives is associated with an acute phase response, since inflammation is important in atherogenesis and may contribute to the thrombo-occlusive complications seen in users of oral contraceptives. \u0000 \u0000Design: Cross-sectional study. \u0000 \u0000Setting: General Community of Augsburg. \u0000 \u0000Subjects: Eight hundred and forty-four women aged 25–44 years, drawn from a random sample of the general population, participating in the MONICA Augsburg survey 1994/95. Two hundred and thirty women used oral contraceptives and 614 did not take any hormones; pregnant women were excluded. \u0000 \u0000Main outcome measures: Plasma C-reactive protein, fibrinogen, and albumin, plasma viscosity and blood cell counts. \u0000 \u0000Results: Age-adjusted plasma levels of C-reactive protein in users of oral contraceptives were almost three times as high as in non-users (2.59 vs. 0.81 mg/l, P<0.001). Conversely, albumin levels were considerably lower in those on oral contraception compared to non-users (40.71 vs. 43.55 g/l,P <0.001). Plasma viscosity was marginally higher in users (P =0.05), but fibrinogen and blood cell counts did not differ between the two groups. The results did not change appreciably after adjustment for other relevant risk factors, including cigarette smoking, body mass index, lipid profile and alcohol consumption, remaining statistically significant at the same level. \u0000 \u0000Conclusion: These results indicate that use of oral contraception is associated with a modest, but statistically highly significant, acute phase response, and may be one mechanism by which oral contraceptives increase thromboembolic risk.","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"1 1","pages":"239-244"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89083238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A link between integrins and MMPs in angiogenesis","authors":"S. Silletti, D. Cheresh","doi":"10.1054/FIPR.2000.0042","DOIUrl":"https://doi.org/10.1054/FIPR.2000.0042","url":null,"abstract":"","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"234 1","pages":"226-238"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75880494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral contraceptive use is associated with a systemic acute phase response","authors":"M. Fröhlich ,&nbsp;A. Döring ,&nbsp;A. Imhof ,&nbsp;W.L. Hutchinson ,&nbsp;M.B. Pepys ,&nbsp;W. Koenig","doi":"10.1054/fipr.1999.0037","DOIUrl":"https://doi.org/10.1054/fipr.1999.0037","url":null,"abstract":"<div><p><em>Objective:</em> We determined whether reported intake of oral contraceptives is associated with an acute phase response, since inflammation is important in atherogenesis and may contribute to the thrombo-occlusive complications seen in users of oral contraceptives.</p><p><em>Design:</em> Cross-sectional study.</p><p><em>Setting:</em> General Community of Augsburg.</p><p><em>Subjects:</em> Eight hundred and forty-four women aged 25–44 years, drawn from a random sample of the general population, participating in the MONICA Augsburg survey 1994/95. Two hundred and thirty women used oral contraceptives and 614 did not take any hormones; pregnant women were excluded.</p><p><em>Main outcome measures:</em> Plasma C-reactive protein, fibrinogen, and albumin, plasma viscosity and blood cell counts.</p><p><em>Results:</em> Age-adjusted plasma levels of C-reactive protein in users of oral contraceptives were almost three times as high as in non-users (2.59 vs. 0.81 mg/l, <em>P</em>&lt;0.001). Conversely, albumin levels were considerably lower in those on oral contraception compared to non-users (40.71 vs. 43.55 g/l,<em>P</em> &lt;0.001). Plasma viscosity was marginally higher in users (<em>P</em> =0.05), but fibrinogen and blood cell counts did not differ between the two groups. The results did not change appreciably after adjustment for other relevant risk factors, including cigarette smoking, body mass index, lipid profile and alcohol consumption, remaining statistically significant at the same level.</p><p><em>Conclusion:</em> These results indicate that use of oral contraception is associated with a modest, but statistically highly significant, acute phase response, and may be one mechanism by which oral contraceptives increase thromboembolic risk.</p></div>","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"13 6","pages":"Pages 239-244"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.1999.0037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71824426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local and systemic changes of fibrinolytic parameters in blood during catheter-directed intra-arterial thrombolysis","authors":"M. Kozak, D. Keber, M. Šabovič","doi":"10.1054/FIPR.2000.0039","DOIUrl":"https://doi.org/10.1054/FIPR.2000.0039","url":null,"abstract":"Abstract Fibrinolytic parameters (plasminogen, fibrinogen, alpha2-antiplasmin, euglobulin clot lysis time and D-dimers) were measured locally near the occlusive peripheral arterial thrombus and in systemic blood of 27 patients treated by catheter-directed thrombolysis with streptokinase. The parameters were measured simultaneously in systemic (venous) and in local (arterial) blood before and 0.5, 1.5, 4, 8, 24 and 48 h after the start of treatment with streptokinase (3750 IU/h). A time-dependent decrease in the concentrations of plasminogen, alpha2-antiplasmin and fibrinogen was measured in both arterial and venous blood, reaching: for plasminogen 39 and 47, for alpha2-antiplasmin 18 and 26, and for fibrinogen 50% and 61%, respectively, of the pretreatment values. A time-dependent increase in D-dimer levels and a shortening of euglobulin clot lysis time were also detected. The differences between time-related arterial and venous samples were significant at least for the first 24 h and became smaller after 48 h of treatment, when at least partial recanalization was achieved in the majority of patients. Our results show that the concentration of plasminogen is significantly reduced during catheter-directed thrombolysis in the systemic blood and even more in the blood surrounding the thrombus. This might reduce the efficacy of intra-arterial catheter-directed thrombolysis.","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"35 1","pages":"259-263"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87027069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}