Opposite regulation by PI3K/Akt and MAPK/ERK pathways of tissue factor expression, cell-associated procoagulant activity and invasiveness in MDA-MB-231 cells

SummaryAn experimental model incorporating cultured endothelial cells (EC) was used to study the "factor VIII bypassing" activity of prothrombin complex concentrates (PCC), a property exploited in the treatment of hemophiliacs with alloantibodies to factor VIII. Two PCC preparations were ineffective as stimuli of tissue factor expression by EC. However, incubation with a combination of PCC plus endotoxin (lipopolysaccharide, LPS) or tumor necrosis factor (TNF) induced much greater tissue factor expression than was seen in response to either substance alone. PCC expressed an additional direct procoagulant activity at the EC surface, which could not be attributed to either thrombin or factor Xa, and which was diminished by an anti-tissue factor antibody. Therefore factor VIIa, which was detectable in both PCC preparations, likely provided this additional direct procoagulant activity at the EC surface. We also excluded the possibility that coagulation proteases contained in or generated in the presence of PCC are protected from inactivation by AT III. Therefore, PCC can indirectly bypass factor VIII by enhancing induced endothelial tissue factor expression, and also possess direct procoagulant activity, probably mediated by factor VIIa.

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Kinetics of lung tissue factor expression and procoagulant activity in bleomycin induced acute lung injury

Clinical and Translational Medicine ◽

10.1186/s40169-015-0063-4 ◽

2015 ◽

Vol 4 (1) ◽

Cited By ~ 4

Author(s):

Li Ma ◽

Ciara M. Shaver ◽

Brandon S. Grove ◽

Daphne B. Mitchell ◽

Nancy E. Wickersham ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Tissue Factor ◽

Lung Tissue ◽

Procoagulant Activity ◽

Tissue Factor Expression ◽

Factor Expression ◽

Kinetics Of

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2526 Irradiation of human monocytic cells is associated with an increase in tissue factor expression and procoagulant activity

European Heart Journal ◽

10.1016/s0195-668x(03)95398-x ◽

2003 ◽

Vol 24 (5) ◽

pp. 475

Author(s):

U RAUCH

Keyword(s):

Tissue Factor ◽

Procoagulant Activity ◽

Tissue Factor Expression ◽

Monocytic Cells ◽

Factor Expression

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Procoagulant Activity of Endothelial Cells after Infection with Respiratory Viruses

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614014 ◽

2000 ◽

Vol 84 (08) ◽

pp. 319-324 ◽

Cited By ~ 65

Author(s):

J. J. M. Bouwman ◽

K. P. Bouter ◽

R. J. A. Diepersloot ◽

Ph. G. de Groot ◽

D. W. Erkelens ◽

...

Keyword(s):

Endothelial Cells ◽

Influenza Virus ◽

Tissue Factor ◽

Respiratory Viruses ◽

Procoagulant Activity ◽

Factor Vii ◽

Influenza B ◽

Tissue Factor Expression ◽

Clotting Time ◽

Factor Expression

SummaryInfluenza virus epidemics are associated with excess mortality due to cardiovascular diseases. There are several case reports of excessive coagulation during generalised influenza virus infection. In this study, we demonstrate the ability of respiratory viruses (influenza A, influenza B, parainfluenza-1, respiratory syncytial virus, adenovirus, cytomegalovirus) to infect lung fibroblasts and human umbilical vein endothelial cells in culture. All viral pathogens induced procoagulant activity in infected endothelial cells, as determined in a one-stage clotting assay, by causing an average 55% reduction in the clotting time. When factor VII deficient plasma was used clotting time was not reduced. The induction of procoagulant activity was associated with a 4- to 5-fold increase in the expression of tissue factor, as measured by the generation of factor Xa. Both experiments indicate that the procoagulant activity of endothelial cells in response to infection with respiratory viruses is caused by upregulation of the extrinsic pathway. Although both enveloped viruses and a non-enveloped virus (adenovirus) induced procoagulant activity in endothelial cells by stimulating tissue factor expression, the role of the viral envelope in the assembly of the prothrombinase complex remains uncertain.We conclude that both enveloped and non-enveloped respiratory viruses are capable of infecting cultured human endothelial cells and causing a shift from anticoagulant to procoagulant activity associated with the induction of tissue factor expression.

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