Binding of tissue plasminogen activator to cultured human endothelial cells.

Hajjar, Katherine A.; Hamel, Nance; Harpel, Peter C.; Nachman, Ralph L.

doi:10.1172/jci113262

Cited by 280 publications

(200 citation statements)

References 41 publications

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“…Immobilization of plasminogen via the lysinebinding sites critically enhances its activation by tissue plasminogen activator and protects plasmin from inactivation by the primary plasmin inhibitor, cr2-antiplasmin [9][10][11][12]. Binding of plasminogen to bacterial fimbriae may thus generate localized plasmin activity on the bacterial surface.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to intravascular fibrinolysis [2], plasmin has been proposed to digest pericellular proteins in inflammatory response [3][4][5], tumor cell invasion [6], ovulation and implantation [7], and neuronal development [8]. Activation of plasminogen by tissue plasminogen activator is kinetically unfavorable in the fluid phase but is remarkably promoted by immobilization of plasminogen via its lysine-binding sites [9][10][11]. Immobilization also protects the activated plasmin from tr2-antiplasmin, which in the fluid phase rapidly inactivates plasmin [11,12].…”

Section: Introductionmentioning

confidence: 99%

“…Activation of plasminogen by tissue plasminogen activator is kinetically unfavorable in the fluid phase but is remarkably promoted by immobilization of plasminogen via its lysine-binding sites [9][10][11]. Immobilization also protects the activated plasmin from tr2-antiplasmin, which in the fluid phase rapidly inactivates plasmin [11,12]. Furthermore, the presence of specific receptors for plasminogen on endothelial cells [11] and inflamCorrespondence address: J. Parkkinen, Department of Medical Chemistry, University of Helsinki, Siltavuorenpenger 10A, SF-00170 Helsinki, Finland…”

Section: Introductionmentioning

confidence: 99%

“…Immobilization also protects the activated plasmin from tr2-antiplasmin, which in the fluid phase rapidly inactivates plasmin [11,12]. Furthermore, the presence of specific receptors for plasminogen on endothelial cells [11] and inflamCorrespondence address: J. Parkkinen, Department of Medical Chemistry, University of Helsinki, Siltavuorenpenger 10A, SF-00170 Helsinki, Finland…”

Section: Introductionmentioning

confidence: 99%

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Binding of plasminogen to Escherichia coli adhesion proteins

Parkkinen

Korhonen

1989

FEBS Letters

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Immobilization of plasminogen via its lysine-binding sites is regarded as a prerequisite for its activation and function in fibrinolysis and pericellular proteolysis. In the present study, the interaction of plasminogen with fimbriae found on Escherichia coli strains causing invasive human infections was studied. Plasminogen displayed concentration-dependent and saturable binding to immobilized type 1 fimbriae and, several fold lower binding to P and S fimbriae. The binding to fimbriae was effectively inhibited by e-aminocaproic acid indicating that it was mediated by the lysine-binding sites of plasminogen. Binding studies with mutated fimbriae and inhibition tests indicated that the interaction was not dependent on the lectin subunit of the fimbriae. These results indicate the existence of a novel type of host-microbe interaction which may be important in the invasion by bacteria of host tissues.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Binding of plasminogen to Escherichia coli adhesion proteins

Parkkinen

Korhonen

1989

FEBS Letters

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“…Kadouri and Bohak (11) suggested a negative feedback-type control for t-PA expression in human lung fibroblasts but did not identify the mechanism by which expression was regulated. Although t-PA has been reported to undergo receptor-mediated binding to a variety of cultured cells (12)(13)(14)(15), the biological significance of this phenomenon remains uncertain. Reports on the internalization and lysosomal degradation of t-PA have been largely confined to studies on hepatocytes, which have a known clearance function (for reviews, see Refs.…”

mentioning

confidence: 99%

Low Density Lipoprotein Receptor-related Protein Modulates the Expression of Tissue-type Plasminogen Activator in Human Colon Fibroblasts

Hardy

Feder

Wolfe

et al. 1997

Journal of Biological Chemistry

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Human colon fibroblasts (HCF) produce tissue-type plasminogen activator (t-PA) in culture, but after 24 -48 h, t-PA ceases to accumulate in the medium. Here, we report negative feedback regulation of t-PA expression, exerted by t-PA or complexes of t-PA with its physiological inhibitor, plasminogen activator inhibitor type 1 (PAI-1). Inhibition of t-PA expression could be induced by addition of exogenous t-PA or t-PA⅐PAI-1 complexes and reversed by monoclonal antibody directed against the active site of t-PA. Analysis of metabolically radiolabeled protein and cellular mRNA showed that both t-PA protein and mRNA levels declined considerably after 24 h. When 125 I-labeled t-PA or t-PA⅐PAI-1 complexes were incubated with HCF, monensin-inhibitable endocytosis and catabolism were observed. The low density lipoprotein receptor-related protein (LRP) was found to be expressed by HCF and to mediate these events. Addition of the 39-kDa receptor-associated protein (RAP), an antagonist for ligand interactions with LRP, removed the block to t-PA expression and restored its accumulation in the medium. Moreover, RAP completely prevented the degradation of exogenous 125 I-labeled t-PA by HCF, suggesting that LRP is the endocytic receptor for t-PA in these cells. These results demonstrate that cellular modulation of t-PA expression in HCF involves LRP receptor-mediated clearance of t-PA. This LRP receptor-mediated event results in down-regulation of t-PA expression at the mRNA level.Fibrinolysis is a complex process that requires precise regulation in vivo to ensure that it is neither deficient nor excessive. The plasminogen activator system is critical for thrombolysis, as well as other physiological processes including cell migration and tissue remodeling (1, 2). Human tissue-type plasminogen activator (t-PA) 1 (M r 68,000), a key serine protease in this system, is of particular pharmacological interest because of its value in the treatment of thromboembolic disorders. Regulation of the plasminogen activator system involves modulation by cofactors and inhibitors as well as controlled synthesis of the key components. It is well documented that t-PA expression is influenced by a variety of exogenous factors such as hormones, growth factors, and cytokines (3-6). Regulation by these factors appears to be receptor-mediated and is imposed at the transcriptional level (7-10). However, information on the role of t-PA in the local regulation of its own biosynthesis, release, and clearance is limited. Kadouri and Bohak (11) suggested a negative feedback-type control for t-PA expression in human lung fibroblasts but did not identify the mechanism by which expression was regulated. Although t-PA has been reported to undergo receptor-mediated binding to a variety of cultured cells (12-15), the biological significance of this phenomenon remains uncertain. Reports on the internalization and lysosomal degradation of t-PA have been largely confined to studies on hepatocytes, which have a known clearance function (for reviews, see Refs. 16,17)....

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Effects of humic acid on the viability and coagulant properties of human umbilical vein endothelial cells

Yang

Chiu

1996

Am. J. Hematol.

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We have previously shown that humic acid (well-water humic acid, HA, and synthetic humic acid, SHA) enhances cell surface expression of tissue factor (TF). Here we report that incubation of human umbilical vein endothelial cells (HUVEC) for 2 hr with HA or SHA cause a rapid rise in TF mRNA levels, as shown by Northern blot analysis. To understand the cytotoxic and fibrinolytic effects of HA and SHA on cultured HUVEC, the cells treated with varying concentrations of HA and SHA for various periods of time. Both HA and SHA (10-200 micrograms/ml) inhibited the viability of subconfluent HUVEC, cultured in the presence or absence of 20% FBS (Fetal Bovine serum) in the culture medium, in a dose-dependent manner. Both HA and SHA induced surface changes in the HUVEC as revealed by scanning electron micrography (SEM). However, protocatechuic acid, the monomer of SHA, did not significantly inhibit cell growth, and showed a cytotoxic effect only at 200 micrograms/ml. Furthermore both HA and SHA stimulated HUVEC to produce plasminogen activator inhibitor (PAI-1) and tissue plasminogen activator (t-PA) in a dose and time dependent fashion; the amount of PAI-1 produced was found to exceed that of t-PA. The monomer of SHA did not have this stimulatory effect. These results distinctly suggest that in addition to the inhibition of viability HA is involved in TF induction and PAI-1 synthesis in HUVEC and these may be some of the plausible mechanisms underlying the thrombotic disorders in Blackfoot disease.

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Binding of tissue plasminogen activator to cultured human endothelial cells.

Cited by 280 publications

References 41 publications

Binding of plasminogen to Escherichia coli adhesion proteins

Binding of plasminogen to Escherichia coli adhesion proteins

Low Density Lipoprotein Receptor-related Protein Modulates the Expression of Tissue-type Plasminogen Activator in Human Colon Fibroblasts

Effects of humic acid on the viability and coagulant properties of human umbilical vein endothelial cells

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