scholarly journals Identification of Urokinase-type Plasminogen Activator Receptor in Human Endothelial Cells and its Modulation by Phorbol Myristate Acetate.

1995 ◽  
Vol 20 (6) ◽  
pp. 429-437 ◽  
Author(s):  
Hiroshi Matsumoto ◽  
Shigeru Ueshima ◽  
Hideharu Fukao ◽  
Youji Mitsui ◽  
Osamu Matsuo
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Phorbol Myristate Acetate ◽  
Human Endothelial Cells ◽  
Myristate Acetate ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Plasminogen Activator Receptor

scholarly journals Tumor necrosis factor induces the production of urokinase-type plasminogen activator by human endothelial cells

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 1991-1998 ◽  
Author(s):  
VW van Hinsbergh ◽  
EA van den Berg ◽  
W Fiers ◽  
G Dooijewaard
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Plasminogen Activator ◽  
Tumor Necrosis ◽  
Tissue Type ◽  
Human Endothelial Cells ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Necrosis Factor ◽  
Pai 1

Abstract Endothelial cells play an important role in the regulation of fibrinolysis by the production of several key regulatory proteins. The cytokines tumor necrosis factor (TNF), lymphotoxin, and interleukin-1 (IL-1), but not interleukin-6, increase the production of plasminogen activator inhibitor-1 (PAI-1) by endothelial cells, whereas they have no stimulatory effect on the production of tissue-type plasminogen activator (t-PA). Primary cultures of human endothelial cells release very little urokinase-type plasminogen activator (u-PA). We report here that TNF and lymphotoxin induce, in a concentration-dependent way, the production of both cellular and secreted u-PA antigen in primary and subcultured human endothelial cells. The TNF-induced increase was accompanied by a more than 10-fold increase in u-PA mRNA. Upon stimulation of early passage umbilical vein endothelial cells by TNF, u- PA was predominantly secreted at the basolateral side, whereas PAI activity and t-PA were found in more equal amounts at the apical and basolateral sides of the cell monolayers. TNF-stimulated u-PA secretion by subcultured human aorta endothelial cells showed only a marginal polarity. The u-PA antigen was present in a plasmin-activatable form (single chain u-PA) and in a nonactivatable form (probably u-PA: PAI-1 complex). During the induction of u-PA by TNF, the ratio between plasmin-activatable u-PA and total u-PA decreased markedly. This may indicate that TNF also increases the degree of u-PA activation. The parallel induction of the synthesis and secretion of both u-PA and PAI- 1 by endothelial cells adds a new aspect to the alterations of the fibrinolytic system caused by inflammatory mediators. This aspect may be significant for the regulation of cell-associated and interstitial plasminogen activator activity.

Tumor necrosis factor induces the production of urokinase-type plasminogen activator by human endothelial cells

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 1991-1998
Author(s):  
VW van Hinsbergh ◽  
EA van den Berg ◽  
W Fiers ◽  
G Dooijewaard
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Plasminogen Activator ◽  
Tumor Necrosis ◽  
Tissue Type ◽  
Human Endothelial Cells ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Necrosis Factor ◽  
Pai 1

Endothelial cells play an important role in the regulation of fibrinolysis by the production of several key regulatory proteins. The cytokines tumor necrosis factor (TNF), lymphotoxin, and interleukin-1 (IL-1), but not interleukin-6, increase the production of plasminogen activator inhibitor-1 (PAI-1) by endothelial cells, whereas they have no stimulatory effect on the production of tissue-type plasminogen activator (t-PA). Primary cultures of human endothelial cells release very little urokinase-type plasminogen activator (u-PA). We report here that TNF and lymphotoxin induce, in a concentration-dependent way, the production of both cellular and secreted u-PA antigen in primary and subcultured human endothelial cells. The TNF-induced increase was accompanied by a more than 10-fold increase in u-PA mRNA. Upon stimulation of early passage umbilical vein endothelial cells by TNF, u- PA was predominantly secreted at the basolateral side, whereas PAI activity and t-PA were found in more equal amounts at the apical and basolateral sides of the cell monolayers. TNF-stimulated u-PA secretion by subcultured human aorta endothelial cells showed only a marginal polarity. The u-PA antigen was present in a plasmin-activatable form (single chain u-PA) and in a nonactivatable form (probably u-PA: PAI-1 complex). During the induction of u-PA by TNF, the ratio between plasmin-activatable u-PA and total u-PA decreased markedly. This may indicate that TNF also increases the degree of u-PA activation. The parallel induction of the synthesis and secretion of both u-PA and PAI- 1 by endothelial cells adds a new aspect to the alterations of the fibrinolytic system caused by inflammatory mediators. This aspect may be significant for the regulation of cell-associated and interstitial plasminogen activator activity.

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