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Nuala A. Booth - One of the best experts on this subject based on the ideXlab platform.

  • Characterization of crosslinking sites in fibrinogen for Plasminogen Activator inhibitor 2 (PAI-2).
    Annals of the New York Academy of Sciences, 2006
    Co-Authors: Helen Ritchie, Laura Catherine Lawrie, Michael W. Mosesson, Nuala A. Booth
    Abstract:

    PAI-2 is a serpin that can be crosslinked to fibrin(ogen) via the Gln-Gln-Ile-Gln sequence (residues 83-86). We have characterized the lysine residues in fibrinogen to which PAI-2 is crosslinked by tissue transglutaminase and factor XIIIa. There was no competition with the crosslinking of alpha 2-antiplasmin, another inhibitor of fibrinolysis, which was specific for Lys 303 in the A alpha chain. PAI-2 was crosslinked to several lysine residues, all in the A alpha chain, 148, 176, 183, 230, 413, and 457, but not to Lys 303. The contrast with alpha 2-antiplasmin was clear from studies with truncated fibrinogens and competition by peptides. This was confirmed and extended by mass spectrometry of peptides after protease digestion of crosslinked products, which identified the lysine residues to which the inhibitors were crosslinked. PAI-2 remained active after cross-linking and inhibited fibrin breakdown, even by two-chain t-PA. Thus, a second inhibitor of fibrinolysis, in addition to alpha 2-antiplasmin, is crosslinked to fibrin and protects it from lysis.

  • Cross-linking of Plasminogen Activator Inhibitor 2 and α2-Antiplasmin to Fibrin(ogen)
    Journal of Biological Chemistry, 2000
    Co-Authors: Helen Ritchie, Laura Catherine Lawrie, Patricia W. Crombie, Michael W. Mosesson, Nuala A. Booth
    Abstract:

    Abstract In this study, we identified lysine residues in the fibrinogen Aα chain that serve as substrates during transglutaminase (TG)-mediated cross-linking of Plasminogen Activator inhibitor 2 (PAI-2). Comparisons were made with α2-antiplasmin (α2-AP), which is known to cross-link to lysine 303 of the Aα chain. A 30-residue peptide containing Lys-303 specifically competed with fibrinogen for cross-linking to α2-AP but not for cross-linking to PAI-2. Further evidence that PAI-2 did not cross-link via Lys-303 was the cross-linking of PAI-2 to I-9 and des-αC fibrinogens, which lack 100 and 390 amino acids from the C terminus of the Aα chain, respectively. PAI-2 or α2-AP was cross-linked to fibrinogen and digested with trypsin or endopeptidase Glu-C, and the resulting peptides analyzed by mass spectrometry. Peptides detected were consistent with tissue TG (tTG)-mediated cross-linking of PAI-2 to lysines 148, 176, 183, 457 and factor XIIIa-mediated cross-linking of PAI-2 to lysines 148, 230, and 413 in the Aα chain. α2-AP was cross-linked only to lysine 303. Cross-linking of PAI-2 to fibrinogen did not compete with α2-AP, and the two proteins utilized different lysines in the Aα chain. Therefore, PAI-2 and α2-AP can cross-link simultaneously to the α polymers of a fibrin clot and promote resistance to lysis.

  • Up-regulation of Plasminogen Activator inhibitor 2 (PAI-2) in response to α-lactalbumin
    Fibrinolysis and Proteolysis, 1999
    Co-Authors: Helen Ritchie, E.a. Schulte, Nuala A. Booth
    Abstract:

    Abstract U937 cells, a monocyte-like cell line, are a potent source of Plasminogen Activator inhibitor 2 (PAI-2) particularly following stimulation with a variety of agents. Lactalbumin enzymatic hydrolysate (LEH) can be used as an alternative to fetal calf serum (FCS) during culture of cells. Here, we report an up-regulation of PAI-2 synthesis following treatment of U937 cells with LEH and purified α-lactalbumin. Secretion of PAI-2 antigen into the culture medium was found to increase over time following growth of U937 cells in medium containing LEH (1 %) compared to medium alone or containing FCS. The possibility that undigested lactalbumin was present in LEH was then examined. A potent increase in secreted and intracellular PAI-2 was seen following stimulation of U937 cells with purified α-lactalbumin. This effect was both dose- and time-dependent. Northern blotting confirmed that the up-regulation in PAI-2 was at the level of mRNA. Basal levels of PAI-2 were up-regulated by an analogue of CAMP, whereas there was no further effect on α-lactalbumin stimulated PAI-2. Lactalbumin is another agent that up-regulates the synthesis of PAI-2, an effect that influences the study of PAI-2 in cultured cells.

  • Monocyte Plasminogen Activator inhibitor 2 (PAI-2) inhibits u-PA-mediated fibrin clot lysis and is cross-linked to fibrin.
    Thrombosis and Haemostasis, 1999
    Co-Authors: Helen Ritchie, Linda A. Robbie, Seonag Kinghorn, Rachel Exley, Nuala A. Booth
    Abstract:

    Plasminogen Activator inhibitor 2 (PAI-2) is a major product of activated human monocytes. Here we show that monocytes inhibited u-PA- but not t-PA-mediated fibrinolysis, by secreting PAI-2 into an overlying fibrin clot. Extracts of arterial and venous human thrombi were found to contain active PAI-2. PAI-2 was cross-linked to fibrin in a reaction catalyzed by two major transglutaminases (TG), tissue TG and factor XIII. The activity of PAI-2 was not affected by such cross-linking. Cross-linking of PAI-2 to fibrin was inhibited by Tridegin, a specific inhibitor of TG, and also by EDTA and iodoacetamide. The use of competitive peptides mimicking the loop between helices C and D of PAI-2 identified Gln 83 and 86 as residues important in cross-linking. This study defines a mechanism by which PAI-2 is localized to fibrin, where it acts as an effective inhibitor of u-PA-mediated fibrinolysis.

  • Secretion of Plasminogen Activator Inhibitor 2 by Human Peripheral Blood Monocytes Occurs via an Endoplasmic Reticulum–Golgi-Independent Pathway
    Experimental Cell Research, 1998
    Co-Authors: Helen Ritchie, Nuala A. Booth
    Abstract:

    Plasminogen Activator inhibitor 2 (PAI-2) is a serine protease inhibitor (serpin) that is secreted and accumulated intracellularly by monocytes. We investigated PAI-2 synthesis by isolated human peripheral blood monocytes and found that a 47-kDa nonglycosylated form of PAI-2 was abundant in conditioned medium from monocytes. Secretion of PAI-2 by monocytes was not inhibited by agents that inhibit either ER-Golgi pathway-dependent secretion, brefeldin A, or N-linked glycosylation, tunicamycin. IL-1beta served as a control for a protein that is secreted by an ER-Golgi-independent pathway, and secretion of IL-1beta was not inhibited by brefeldin A. This was in contrast to secretion of TNFalpha, which was dependent on the ER-Golgi pathway. None of the treatments was cytotoxic toward monocytes, as measured by release of the intracellular enzyme lactate dehydrogenase (LDH) into the conditioned medium. Subcellular fractionation revealed that PAI-2 and IL-1beta were colocalized. The mechanism for secretion of PAI-2 was not dependent on calcium or intracellular trafficking via the classical vesicular mechanism(s), distinguishing it from IL-1beta secretion. These studies show that PAI-2 is secreted by primary human monocytes via an ER-Golgi-independent pathway.

Meral Gunhan - One of the best experts on this subject based on the ideXlab platform.

  • gingival crevicular fluid tissue blood vessel type Plasminogen Activator and Plasminogen Activator inhibitor 2 levels in patients with rheumatoid arthritis effects of nonsurgical periodontal therapy
    Journal of Periodontal Research, 2017
    Co-Authors: şivge Kurgan, Muhittin Serdar, Canan Onder, N Balci, Ozlem Fentoglu, F Eser, M Balseven, Dimitris N Tatakis, Meral Gunhan
    Abstract:

    Background and Objective The aim of this study was to evaluate the effect of nonsurgical periodontal therapy on clinical parameters and gingival crevicular fluid levels of tissue/blood vessel-type Plasminogen Activator (t-PA) and Plasminogen Activator Inhibitor-2 (PAI-2) in patients with periodontitis, with or without rheumatoid arthritis (RA). Material and Methods Fifteen patients with RA and chronic periodontitis (RA-P), 15 systemically healthy patients with chronic periodontitis (H-P) and 15 periodontally and systemically healthy volunteers (C) were included in the study. Plaque index, gingival index, probing pocket depth, clinical attachment level, bleeding on probing, gingival crevicular fluid t-PA and PAI-2 levels, erythrocyte sedimentation rate, serum C-reactive protein and disease activity score were evaluated at baseline and 3 mo after mechanical nonsurgical periodontal therapy. Results All periodontal clinical parameters were significantly higher in the RA-P and H-P groups compared with the C group (p < 0.001) and decreased significantly after treatment (p < 0.001). Pretreatment t-PA levels were highest in the RA-P group and significantly decreased post-treatment (p = 0.047). Pre- and post-treatment PAI-2 levels were significantly lower in controls compared with both periodontitis groups (p < 0.05). Gingival crevicular fluid volume and the levels of t-PA and PAI-2 were significantly correlated. Conclusion In patients with periodontitis and RA, nonsurgical periodontal therapy reduced the pretreatment gingival crevicular fluid t-PA levels, which were significantly correlated with gingival crevicular fluid PAI-2 levels. The significantly higher t-PA and PAI-2 gingival crevicular fluid levels in periodontal patients, regardless of systemic status, suggest that the Plasminogen activating system plays a role in the disease process of periodontitis.

  • Gingival crevicular fluid tissue/blood vessel‐type Plasminogen Activator and Plasminogen Activator inhibitor‐2 levels in patients with rheumatoid arthritis: effects of nonsurgical periodontal therapy
    Journal of Periodontal Research, 2016
    Co-Authors: şivge Kurgan, Muhittin Serdar, Canan Onder, N Balci, Ozlem Fentoglu, F Eser, M Balseven, Dimitris N Tatakis, Meral Gunhan
    Abstract:

    Background and Objective The aim of this study was to evaluate the effect of nonsurgical periodontal therapy on clinical parameters and gingival crevicular fluid levels of tissue/blood vessel-type Plasminogen Activator (t-PA) and Plasminogen Activator Inhibitor-2 (PAI-2) in patients with periodontitis, with or without rheumatoid arthritis (RA). Material and Methods Fifteen patients with RA and chronic periodontitis (RA-P), 15 systemically healthy patients with chronic periodontitis (H-P) and 15 periodontally and systemically healthy volunteers (C) were included in the study. Plaque index, gingival index, probing pocket depth, clinical attachment level, bleeding on probing, gingival crevicular fluid t-PA and PAI-2 levels, erythrocyte sedimentation rate, serum C-reactive protein and disease activity score were evaluated at baseline and 3 mo after mechanical nonsurgical periodontal therapy. Results All periodontal clinical parameters were significantly higher in the RA-P and H-P groups compared with the C group (p < 0.001) and decreased significantly after treatment (p < 0.001). Pretreatment t-PA levels were highest in the RA-P group and significantly decreased post-treatment (p = 0.047). Pre- and post-treatment PAI-2 levels were significantly lower in controls compared with both periodontitis groups (p < 0.05). Gingival crevicular fluid volume and the levels of t-PA and PAI-2 were significantly correlated. Conclusion In patients with periodontitis and RA, nonsurgical periodontal therapy reduced the pretreatment gingival crevicular fluid t-PA levels, which were significantly correlated with gingival crevicular fluid PAI-2 levels. The significantly higher t-PA and PAI-2 gingival crevicular fluid levels in periodontal patients, regardless of systemic status, suggest that the Plasminogen activating system plays a role in the disease process of periodontitis.

Muhittin Serdar - One of the best experts on this subject based on the ideXlab platform.

  • gingival crevicular fluid tissue blood vessel type Plasminogen Activator and Plasminogen Activator inhibitor 2 levels in patients with rheumatoid arthritis effects of nonsurgical periodontal therapy
    Journal of Periodontal Research, 2017
    Co-Authors: şivge Kurgan, Muhittin Serdar, Canan Onder, N Balci, Ozlem Fentoglu, F Eser, M Balseven, Dimitris N Tatakis, Meral Gunhan
    Abstract:

    Background and Objective The aim of this study was to evaluate the effect of nonsurgical periodontal therapy on clinical parameters and gingival crevicular fluid levels of tissue/blood vessel-type Plasminogen Activator (t-PA) and Plasminogen Activator Inhibitor-2 (PAI-2) in patients with periodontitis, with or without rheumatoid arthritis (RA). Material and Methods Fifteen patients with RA and chronic periodontitis (RA-P), 15 systemically healthy patients with chronic periodontitis (H-P) and 15 periodontally and systemically healthy volunteers (C) were included in the study. Plaque index, gingival index, probing pocket depth, clinical attachment level, bleeding on probing, gingival crevicular fluid t-PA and PAI-2 levels, erythrocyte sedimentation rate, serum C-reactive protein and disease activity score were evaluated at baseline and 3 mo after mechanical nonsurgical periodontal therapy. Results All periodontal clinical parameters were significantly higher in the RA-P and H-P groups compared with the C group (p < 0.001) and decreased significantly after treatment (p < 0.001). Pretreatment t-PA levels were highest in the RA-P group and significantly decreased post-treatment (p = 0.047). Pre- and post-treatment PAI-2 levels were significantly lower in controls compared with both periodontitis groups (p < 0.05). Gingival crevicular fluid volume and the levels of t-PA and PAI-2 were significantly correlated. Conclusion In patients with periodontitis and RA, nonsurgical periodontal therapy reduced the pretreatment gingival crevicular fluid t-PA levels, which were significantly correlated with gingival crevicular fluid PAI-2 levels. The significantly higher t-PA and PAI-2 gingival crevicular fluid levels in periodontal patients, regardless of systemic status, suggest that the Plasminogen activating system plays a role in the disease process of periodontitis.

  • Gingival crevicular fluid tissue/blood vessel‐type Plasminogen Activator and Plasminogen Activator inhibitor‐2 levels in patients with rheumatoid arthritis: effects of nonsurgical periodontal therapy
    Journal of Periodontal Research, 2016
    Co-Authors: şivge Kurgan, Muhittin Serdar, Canan Onder, N Balci, Ozlem Fentoglu, F Eser, M Balseven, Dimitris N Tatakis, Meral Gunhan
    Abstract:

    Background and Objective The aim of this study was to evaluate the effect of nonsurgical periodontal therapy on clinical parameters and gingival crevicular fluid levels of tissue/blood vessel-type Plasminogen Activator (t-PA) and Plasminogen Activator Inhibitor-2 (PAI-2) in patients with periodontitis, with or without rheumatoid arthritis (RA). Material and Methods Fifteen patients with RA and chronic periodontitis (RA-P), 15 systemically healthy patients with chronic periodontitis (H-P) and 15 periodontally and systemically healthy volunteers (C) were included in the study. Plaque index, gingival index, probing pocket depth, clinical attachment level, bleeding on probing, gingival crevicular fluid t-PA and PAI-2 levels, erythrocyte sedimentation rate, serum C-reactive protein and disease activity score were evaluated at baseline and 3 mo after mechanical nonsurgical periodontal therapy. Results All periodontal clinical parameters were significantly higher in the RA-P and H-P groups compared with the C group (p < 0.001) and decreased significantly after treatment (p < 0.001). Pretreatment t-PA levels were highest in the RA-P group and significantly decreased post-treatment (p = 0.047). Pre- and post-treatment PAI-2 levels were significantly lower in controls compared with both periodontitis groups (p < 0.05). Gingival crevicular fluid volume and the levels of t-PA and PAI-2 were significantly correlated. Conclusion In patients with periodontitis and RA, nonsurgical periodontal therapy reduced the pretreatment gingival crevicular fluid t-PA levels, which were significantly correlated with gingival crevicular fluid PAI-2 levels. The significantly higher t-PA and PAI-2 gingival crevicular fluid levels in periodontal patients, regardless of systemic status, suggest that the Plasminogen activating system plays a role in the disease process of periodontitis.

  • evaluation of gingival crevicular fluid levels of tissue Plasminogen Activator Plasminogen Activator inhibitor 2 matrix metalloproteinase 3 and interleukin 1 β in patients with different periodontal diseases
    Journal of Periodontal Research, 2015
    Co-Authors: Utku Toyman, Gülay Tüter, Bülent Kurtiş, E. Kıvrak, Ş. Bozkurt, Ayşegül Yücel, Muhittin Serdar
    Abstract:

    Objectives The purpose of this study was to evaluate the gingival crevicular fluid levels of interleukin-1beta (IL-1β), matrix metalloproteinases-3 (MMP-3), tissue type Plasminogen Activator (t-PA) and Plasminogen Activator inhibitor 2 (PAI-2) in patients with chronic periodontitis, aggressive periodontitis (AgP) and healthy individuals (controls). Material and Methods Systemically healthy (21 chronic periodontitis, 23 AgP and 20 controls) subjects were included in this study. Plaque index, gingival index, probing pocket depth and clinical attachment level were recorded and gingival crevicular fluid samples were collected. Assays for IL-1β, MMP-3, t-PA and PAI-2 levels in gingival crevicular fluid were carried out by an enzyme-linked immunosorbent assay. The one-sample Kolmogorov–Smirnov test, Mann–Whitney U test and Spearman correlation coefficient were used for data analyses. Results Gingival crevicular fluid levels of t-PA and IL-1β were significantly higher in chronic periodontitis and AgP groups than in the control group (p < 0.001). MMP-3 levels in gingival crevicular fluid were detected as significantly higher in the chronic periodontitis and AgP groups compared with the control group (p < 0.05). The t-PA/PAI-2 rate of patients with chronic periodontitis and AgP were significantly higher than the control group (p < 0.05). The positive correlations were found among the PAI-2, t-PA, IL-1β and MMP-3 levels in gingival crevicular fluid. The volume of the gingival crevicular fluid correlated with all of the clinical parameters (p < 0.001). There were positive correlations between the gingival crevicular fluid levels of PAI-2 and the probing pocket depth and between gingival crevicular fluid levels of PAI-2 and the clinical attachment level (p < 0.01). Similarly, significant correlations were found between t-PA levels and probing pocket depth and between t-PA levels and clinical attachment level measurements (p < 0.001). Conclusion The present data showed that gingival crevicular fluid levels of IL-1 β, MMP-3 and t-PA increased in periodontal disease regardless of the periodontitis type and played a part in tissue destruction.

  • Evaluation of gingival crevicular fluid levels of tissue Plasminogen Activator, Plasminogen Activator inhibitor 2, matrix metalloproteinase-3 and interleukin 1-β in patients with different periodontal diseases.
    Journal of Periodontal Research, 2014
    Co-Authors: Utku Toyman, Gülay Tüter, Bülent Kurtiş, E. Kıvrak, Ş. Bozkurt, Ayşegül Yücel, Muhittin Serdar
    Abstract:

    Objectives The purpose of this study was to evaluate the gingival crevicular fluid levels of interleukin-1beta (IL-1β), matrix metalloproteinases-3 (MMP-3), tissue type Plasminogen Activator (t-PA) and Plasminogen Activator inhibitor 2 (PAI-2) in patients with chronic periodontitis, aggressive periodontitis (AgP) and healthy individuals (controls). Material and Methods Systemically healthy (21 chronic periodontitis, 23 AgP and 20 controls) subjects were included in this study. Plaque index, gingival index, probing pocket depth and clinical attachment level were recorded and gingival crevicular fluid samples were collected. Assays for IL-1β, MMP-3, t-PA and PAI-2 levels in gingival crevicular fluid were carried out by an enzyme-linked immunosorbent assay. The one-sample Kolmogorov–Smirnov test, Mann–Whitney U test and Spearman correlation coefficient were used for data analyses. Results Gingival crevicular fluid levels of t-PA and IL-1β were significantly higher in chronic periodontitis and AgP groups than in the control group (p 

  • Short term effects of non-surgical periodontal treatment on gingival crevicular fluid levels of tissue Plasminogen Activator (t-PA) and Plasminogen Activator inhibitor 2 (PAI-2) in patients with chronic and aggressive periodontitis.
    Archives of Oral Biology, 2013
    Co-Authors: Gülay Tüter, Bülent Kurtiş, Ayşegül Yücel, Muhittin Serdar, Burcu Özdemir, Eylem Ayhan
    Abstract:

    a b s t r a c t Objective: The purpose of this study was to evaluate the gingival crevicular fluid (GCF) levels of tissue type Plasminogen Activator (t-PA) and Plasminogen Activator inhibitor 2 (PAI-2) in aggressive periodontitis (AgP), chronic periodontitis (CP) and periodontally healthy control subjects, before (BT) and after (AT) the non-surgical periodontal treatment. Design: Systemically healthy 12 CP and 13 AgP patients and 20 control subjects were included in this study. Plaque index, gingival index, probing depth and clinical attachment levels were recorded and GCF samples were collected BT and AT. Assays for GCF t-PA and PAI-2 levels were carried out by an enzyme linked immunosorbent assay (ELISA). The x 2 , Wilcoxon and Mann‐ Whitney U tests and Spearman correlation coefficient were used for data analyses. Results: Statistically significant reductions in clinical index scores were noted in both periodontitis groups after treatment. No significant differences were detected in GCF levels of t-PA and PAI-2 between CP and AgP groups at either BT or AT. There was a statistically significant decrease in GCF PAI-2 levels in CP after therapy ( p < 0.01). GCF t-PA levels in CP and AgP groups exhibited significant correlations with PD and CAL measurements at both BT and AT ( p < 0.01). Conclusion: Significant decrease was detected for GCF PAI-2 levels in CP and clinical parameters in both CP and AgP by non-surgical periodontal treatment.

Helen Ritchie - One of the best experts on this subject based on the ideXlab platform.

  • Characterization of crosslinking sites in fibrinogen for Plasminogen Activator inhibitor 2 (PAI-2).
    Annals of the New York Academy of Sciences, 2006
    Co-Authors: Helen Ritchie, Laura Catherine Lawrie, Michael W. Mosesson, Nuala A. Booth
    Abstract:

    PAI-2 is a serpin that can be crosslinked to fibrin(ogen) via the Gln-Gln-Ile-Gln sequence (residues 83-86). We have characterized the lysine residues in fibrinogen to which PAI-2 is crosslinked by tissue transglutaminase and factor XIIIa. There was no competition with the crosslinking of alpha 2-antiplasmin, another inhibitor of fibrinolysis, which was specific for Lys 303 in the A alpha chain. PAI-2 was crosslinked to several lysine residues, all in the A alpha chain, 148, 176, 183, 230, 413, and 457, but not to Lys 303. The contrast with alpha 2-antiplasmin was clear from studies with truncated fibrinogens and competition by peptides. This was confirmed and extended by mass spectrometry of peptides after protease digestion of crosslinked products, which identified the lysine residues to which the inhibitors were crosslinked. PAI-2 remained active after cross-linking and inhibited fibrin breakdown, even by two-chain t-PA. Thus, a second inhibitor of fibrinolysis, in addition to alpha 2-antiplasmin, is crosslinked to fibrin and protects it from lysis.

  • Cross-linking of Plasminogen Activator Inhibitor 2 and α2-Antiplasmin to Fibrin(ogen)
    Journal of Biological Chemistry, 2000
    Co-Authors: Helen Ritchie, Laura Catherine Lawrie, Patricia W. Crombie, Michael W. Mosesson, Nuala A. Booth
    Abstract:

    Abstract In this study, we identified lysine residues in the fibrinogen Aα chain that serve as substrates during transglutaminase (TG)-mediated cross-linking of Plasminogen Activator inhibitor 2 (PAI-2). Comparisons were made with α2-antiplasmin (α2-AP), which is known to cross-link to lysine 303 of the Aα chain. A 30-residue peptide containing Lys-303 specifically competed with fibrinogen for cross-linking to α2-AP but not for cross-linking to PAI-2. Further evidence that PAI-2 did not cross-link via Lys-303 was the cross-linking of PAI-2 to I-9 and des-αC fibrinogens, which lack 100 and 390 amino acids from the C terminus of the Aα chain, respectively. PAI-2 or α2-AP was cross-linked to fibrinogen and digested with trypsin or endopeptidase Glu-C, and the resulting peptides analyzed by mass spectrometry. Peptides detected were consistent with tissue TG (tTG)-mediated cross-linking of PAI-2 to lysines 148, 176, 183, 457 and factor XIIIa-mediated cross-linking of PAI-2 to lysines 148, 230, and 413 in the Aα chain. α2-AP was cross-linked only to lysine 303. Cross-linking of PAI-2 to fibrinogen did not compete with α2-AP, and the two proteins utilized different lysines in the Aα chain. Therefore, PAI-2 and α2-AP can cross-link simultaneously to the α polymers of a fibrin clot and promote resistance to lysis.

  • Thrombin inhibits apoptosis of monocytes and Plasminogen Activator inhibitor 2 (PAI-2) is not responsible for this inhibition.
    Experimental Cell Research, 2000
    Co-Authors: Helen Ritchie, Alex Fragoyannis
    Abstract:

    Plasminogen Activator inhibitor 2 (PAI-2) has been shown to inhibit apoptosis in transfected cells. We have investigated this phenomenon in activated human monocytes, which are a physiological source of intracellular PAI-2. Apoptosis of monocytes was rapidly induced by removal of serum, addition of hydrogen peroxide, or binding of a monoclonal antibody to Fas. Treatment of monocytes with thrombin or lipopolysaccharide (LPS) inhibited apoptosis of monocytes and also up-regulated intracellular PAI-2. Increased apoptosis was accompanied with increased activity of caspases 3 and 8. Thrombin or LPS treatment of monocytes decreased the activity of both caspases, which correlated with protection from apoptosis. The role for PAI-2 in protection of monocytes from apoptosis was studied. Monocytes were transfected with antisense oligonucleotides that blocked PAI-2 antigen, and antisense for PAI-2 had no effect on apoptosis of monocytes. No interaction was evident between PAI-2 and recombinant caspases 3 and 8 in vitro. PAI-2 was not a substrate for caspases during apoptosis of monocytes, although some cleavage of recombinant PAI-2 by caspase 3 was evident in vitro. This study shows that thrombin or LPS protected monocytes from apoptosis and that PAI-2 did not mediate this inhibitory effect.

  • Up-regulation of Plasminogen Activator inhibitor 2 (PAI-2) in response to α-lactalbumin
    Fibrinolysis and Proteolysis, 1999
    Co-Authors: Helen Ritchie, E.a. Schulte, Nuala A. Booth
    Abstract:

    Abstract U937 cells, a monocyte-like cell line, are a potent source of Plasminogen Activator inhibitor 2 (PAI-2) particularly following stimulation with a variety of agents. Lactalbumin enzymatic hydrolysate (LEH) can be used as an alternative to fetal calf serum (FCS) during culture of cells. Here, we report an up-regulation of PAI-2 synthesis following treatment of U937 cells with LEH and purified α-lactalbumin. Secretion of PAI-2 antigen into the culture medium was found to increase over time following growth of U937 cells in medium containing LEH (1 %) compared to medium alone or containing FCS. The possibility that undigested lactalbumin was present in LEH was then examined. A potent increase in secreted and intracellular PAI-2 was seen following stimulation of U937 cells with purified α-lactalbumin. This effect was both dose- and time-dependent. Northern blotting confirmed that the up-regulation in PAI-2 was at the level of mRNA. Basal levels of PAI-2 were up-regulated by an analogue of CAMP, whereas there was no further effect on α-lactalbumin stimulated PAI-2. Lactalbumin is another agent that up-regulates the synthesis of PAI-2, an effect that influences the study of PAI-2 in cultured cells.

  • Monocyte Plasminogen Activator inhibitor 2 (PAI-2) inhibits u-PA-mediated fibrin clot lysis and is cross-linked to fibrin.
    Thrombosis and Haemostasis, 1999
    Co-Authors: Helen Ritchie, Linda A. Robbie, Seonag Kinghorn, Rachel Exley, Nuala A. Booth
    Abstract:

    Plasminogen Activator inhibitor 2 (PAI-2) is a major product of activated human monocytes. Here we show that monocytes inhibited u-PA- but not t-PA-mediated fibrinolysis, by secreting PAI-2 into an overlying fibrin clot. Extracts of arterial and venous human thrombi were found to contain active PAI-2. PAI-2 was cross-linked to fibrin in a reaction catalyzed by two major transglutaminases (TG), tissue TG and factor XIII. The activity of PAI-2 was not affected by such cross-linking. Cross-linking of PAI-2 to fibrin was inhibited by Tridegin, a specific inhibitor of TG, and also by EDTA and iodoacetamide. The use of competitive peptides mimicking the loop between helices C and D of PAI-2 identified Gln 83 and 86 as residues important in cross-linking. This study defines a mechanism by which PAI-2 is localized to fibrin, where it acts as an effective inhibitor of u-PA-mediated fibrinolysis.

şivge Kurgan - One of the best experts on this subject based on the ideXlab platform.

  • gingival crevicular fluid tissue blood vessel type Plasminogen Activator and Plasminogen Activator inhibitor 2 levels in patients with rheumatoid arthritis effects of nonsurgical periodontal therapy
    Journal of Periodontal Research, 2017
    Co-Authors: şivge Kurgan, Muhittin Serdar, Canan Onder, N Balci, Ozlem Fentoglu, F Eser, M Balseven, Dimitris N Tatakis, Meral Gunhan
    Abstract:

    Background and Objective The aim of this study was to evaluate the effect of nonsurgical periodontal therapy on clinical parameters and gingival crevicular fluid levels of tissue/blood vessel-type Plasminogen Activator (t-PA) and Plasminogen Activator Inhibitor-2 (PAI-2) in patients with periodontitis, with or without rheumatoid arthritis (RA). Material and Methods Fifteen patients with RA and chronic periodontitis (RA-P), 15 systemically healthy patients with chronic periodontitis (H-P) and 15 periodontally and systemically healthy volunteers (C) were included in the study. Plaque index, gingival index, probing pocket depth, clinical attachment level, bleeding on probing, gingival crevicular fluid t-PA and PAI-2 levels, erythrocyte sedimentation rate, serum C-reactive protein and disease activity score were evaluated at baseline and 3 mo after mechanical nonsurgical periodontal therapy. Results All periodontal clinical parameters were significantly higher in the RA-P and H-P groups compared with the C group (p < 0.001) and decreased significantly after treatment (p < 0.001). Pretreatment t-PA levels were highest in the RA-P group and significantly decreased post-treatment (p = 0.047). Pre- and post-treatment PAI-2 levels were significantly lower in controls compared with both periodontitis groups (p < 0.05). Gingival crevicular fluid volume and the levels of t-PA and PAI-2 were significantly correlated. Conclusion In patients with periodontitis and RA, nonsurgical periodontal therapy reduced the pretreatment gingival crevicular fluid t-PA levels, which were significantly correlated with gingival crevicular fluid PAI-2 levels. The significantly higher t-PA and PAI-2 gingival crevicular fluid levels in periodontal patients, regardless of systemic status, suggest that the Plasminogen activating system plays a role in the disease process of periodontitis.

  • Gingival crevicular fluid tissue/blood vessel‐type Plasminogen Activator and Plasminogen Activator inhibitor‐2 levels in patients with rheumatoid arthritis: effects of nonsurgical periodontal therapy
    Journal of Periodontal Research, 2016
    Co-Authors: şivge Kurgan, Muhittin Serdar, Canan Onder, N Balci, Ozlem Fentoglu, F Eser, M Balseven, Dimitris N Tatakis, Meral Gunhan
    Abstract:

    Background and Objective The aim of this study was to evaluate the effect of nonsurgical periodontal therapy on clinical parameters and gingival crevicular fluid levels of tissue/blood vessel-type Plasminogen Activator (t-PA) and Plasminogen Activator Inhibitor-2 (PAI-2) in patients with periodontitis, with or without rheumatoid arthritis (RA). Material and Methods Fifteen patients with RA and chronic periodontitis (RA-P), 15 systemically healthy patients with chronic periodontitis (H-P) and 15 periodontally and systemically healthy volunteers (C) were included in the study. Plaque index, gingival index, probing pocket depth, clinical attachment level, bleeding on probing, gingival crevicular fluid t-PA and PAI-2 levels, erythrocyte sedimentation rate, serum C-reactive protein and disease activity score were evaluated at baseline and 3 mo after mechanical nonsurgical periodontal therapy. Results All periodontal clinical parameters were significantly higher in the RA-P and H-P groups compared with the C group (p < 0.001) and decreased significantly after treatment (p < 0.001). Pretreatment t-PA levels were highest in the RA-P group and significantly decreased post-treatment (p = 0.047). Pre- and post-treatment PAI-2 levels were significantly lower in controls compared with both periodontitis groups (p < 0.05). Gingival crevicular fluid volume and the levels of t-PA and PAI-2 were significantly correlated. Conclusion In patients with periodontitis and RA, nonsurgical periodontal therapy reduced the pretreatment gingival crevicular fluid t-PA levels, which were significantly correlated with gingival crevicular fluid PAI-2 levels. The significantly higher t-PA and PAI-2 gingival crevicular fluid levels in periodontal patients, regardless of systemic status, suggest that the Plasminogen activating system plays a role in the disease process of periodontitis.