Specificity of the thrombin-induced release of tissue plasminogen activator from cultured human endothelial cells

E. G. Levin, David Stern, P. P. Nawroth, R. A. Marlar, D. S. Fair, J. W. Fenton, L. A. Harker

Research output: Contribution to journalArticle

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Abstract

The addition of thrombin (9 nM) to primary cultures of human endothelial cells induces a 6- to 7-fold increase in the rate of release of tissue plasminogen activator (tPA). Several other serine proteases which specifically interact with endothelial cells were also analyzed for their effect on tPA release. Gamma-thrombin, an autocatalytic product of α-thrombin, promoted tPA release but was less effective than α-thrombin. A maximum increase of 5.5-fold was observed, although a concentration of γ-thrombin 20 times greater than α-thrombin was required. The response to Factor X(a) was similar to α-thrombin, although the stimulation was significantly reduced by the addition of hirudin or DAPA suggesting that prothrombin activation was occurring. The simultaneous addition of prothrombin with Factor X(a) resulted in enhanced tPA release equal to that observed with an equimolar concentration of active α-thrombin. Thus, under these conditions, Factor X(a)-cell surface mediated activation of prothrombin can lead to a secondary effect resulting from cell-thrombin interaction. Activated protein C, which has been implicated as a pro-fibrinolytic agent, was also tested. No change in tPA release occurred after the addition of up to 325 nM activated protein C in the presence or absence of proteins. Factor IX(a) and plasmin were also ineffective. The effect of thrombin on the endothelial cell derived plasminogen activator specific inhibitor was also studied. Thrombin produced a small but variable release of the inhibitor with an increase of less than twice that of non-thrombin treated controls.

Original languageEnglish (US)
Pages (from-to)115-119
Number of pages5
JournalThrombosis and Haemostasis
Volume56
Issue number2
StatePublished - 1986
Externally publishedYes

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Tissue Plasminogen Activator
Thrombin
Endothelial Cells
Factor X
Prothrombin
Protein C
Thrombin Time
Hirudins
Plasminogen Inactivators
Factor IX
Fibrinolytic Agents
Fibrinolysin
Serine Proteases
Cell Communication

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Levin, E. G., Stern, D., Nawroth, P. P., Marlar, R. A., Fair, D. S., Fenton, J. W., & Harker, L. A. (1986). Specificity of the thrombin-induced release of tissue plasminogen activator from cultured human endothelial cells. Thrombosis and Haemostasis, 56(2), 115-119.

Specificity of the thrombin-induced release of tissue plasminogen activator from cultured human endothelial cells. / Levin, E. G.; Stern, David; Nawroth, P. P.; Marlar, R. A.; Fair, D. S.; Fenton, J. W.; Harker, L. A.

In: Thrombosis and Haemostasis, Vol. 56, No. 2, 1986, p. 115-119.

Research output: Contribution to journalArticle

Levin, EG, Stern, D, Nawroth, PP, Marlar, RA, Fair, DS, Fenton, JW & Harker, LA 1986, 'Specificity of the thrombin-induced release of tissue plasminogen activator from cultured human endothelial cells', Thrombosis and Haemostasis, vol. 56, no. 2, pp. 115-119.
Levin, E. G. ; Stern, David ; Nawroth, P. P. ; Marlar, R. A. ; Fair, D. S. ; Fenton, J. W. ; Harker, L. A. / Specificity of the thrombin-induced release of tissue plasminogen activator from cultured human endothelial cells. In: Thrombosis and Haemostasis. 1986 ; Vol. 56, No. 2. pp. 115-119.
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N2 - The addition of thrombin (9 nM) to primary cultures of human endothelial cells induces a 6- to 7-fold increase in the rate of release of tissue plasminogen activator (tPA). Several other serine proteases which specifically interact with endothelial cells were also analyzed for their effect on tPA release. Gamma-thrombin, an autocatalytic product of α-thrombin, promoted tPA release but was less effective than α-thrombin. A maximum increase of 5.5-fold was observed, although a concentration of γ-thrombin 20 times greater than α-thrombin was required. The response to Factor X(a) was similar to α-thrombin, although the stimulation was significantly reduced by the addition of hirudin or DAPA suggesting that prothrombin activation was occurring. The simultaneous addition of prothrombin with Factor X(a) resulted in enhanced tPA release equal to that observed with an equimolar concentration of active α-thrombin. Thus, under these conditions, Factor X(a)-cell surface mediated activation of prothrombin can lead to a secondary effect resulting from cell-thrombin interaction. Activated protein C, which has been implicated as a pro-fibrinolytic agent, was also tested. No change in tPA release occurred after the addition of up to 325 nM activated protein C in the presence or absence of proteins. Factor IX(a) and plasmin were also ineffective. The effect of thrombin on the endothelial cell derived plasminogen activator specific inhibitor was also studied. Thrombin produced a small but variable release of the inhibitor with an increase of less than twice that of non-thrombin treated controls.

AB - The addition of thrombin (9 nM) to primary cultures of human endothelial cells induces a 6- to 7-fold increase in the rate of release of tissue plasminogen activator (tPA). Several other serine proteases which specifically interact with endothelial cells were also analyzed for their effect on tPA release. Gamma-thrombin, an autocatalytic product of α-thrombin, promoted tPA release but was less effective than α-thrombin. A maximum increase of 5.5-fold was observed, although a concentration of γ-thrombin 20 times greater than α-thrombin was required. The response to Factor X(a) was similar to α-thrombin, although the stimulation was significantly reduced by the addition of hirudin or DAPA suggesting that prothrombin activation was occurring. The simultaneous addition of prothrombin with Factor X(a) resulted in enhanced tPA release equal to that observed with an equimolar concentration of active α-thrombin. Thus, under these conditions, Factor X(a)-cell surface mediated activation of prothrombin can lead to a secondary effect resulting from cell-thrombin interaction. Activated protein C, which has been implicated as a pro-fibrinolytic agent, was also tested. No change in tPA release occurred after the addition of up to 325 nM activated protein C in the presence or absence of proteins. Factor IX(a) and plasmin were also ineffective. The effect of thrombin on the endothelial cell derived plasminogen activator specific inhibitor was also studied. Thrombin produced a small but variable release of the inhibitor with an increase of less than twice that of non-thrombin treated controls.

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