Studies of the Activation of Factor VII Bound to Tissue Factor

Experiments were performed to evaluate activation of factor VII bound to relipidated tissue factor (TF) in suspension and to TF constitutively expressed on the surface of an ovarian carcinoma cell line (OC-2008). Activation was assessed by measuring cleavage of 125l-factor VII and by the ability of...

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Bibliographic Details
Published in:Blood 1996-05, Vol.87 (9), p.3738-3748
Main Authors: Mohan Rao, L.Vijaya, Williams, Todd, Rapaport, Samuel I.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Blood coagulation. Blood cells
Cell Membrane - metabolism
Coagulation factors
Factor VII - metabolism
Female
Fundamental and applied biological sciences. Psychology
Humans
Molecular and cellular biology
Protein Binding
Thromboplastin - metabolism
Tumor Cells, Cultured
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Summary:Experiments were performed to evaluate activation of factor VII bound to relipidated tissue factor (TF) in suspension and to TF constitutively expressed on the surface of an ovarian carcinoma cell line (OC-2008). Activation was assessed by measuring cleavage of 125l-factor VII and by the ability of unlabeled factor VII to catalyze activation of a variant factor IX molecule that, after activation, cannot back-activate factor VII. Factor Xa was found to effectively activate factor VII bound to TF relipidated in either acidic or neutral phospholipid vesicles. Autoactivation of factor VII bound to TF in suspension was dependent on the preparation of TF apoprotein used and the technique of its relipidation. This highlights the need for caution in extrapolating data from TF in suspension to the activation of factor VII bound to cell surfaces during hemostasis. A relatively slow activation of factor VII bound to OC-2008 monolayers in the absence of added protease was observed consistently. Antithrombin in the presence or absence of heparin prevented this basal activation, whereas TF pathway inhibitor (TFPD/factor Xa complexes had only a limited inhibitory effect. Adding a substrate concentration of factor X markedly enhanced basal activation of factor VII. but both TFPI/factor Xa and anti-thrombin/heparin abolished this enhancement. Overall, our data are compatible with the hypothesis that not all factor VII/TF complexes formed at a site of tissue injury are readily activated to factor VIIa (Vlla)/TF complexes during hemostasis. The clinical significance of this is discussed.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V87.9.3738.bloodjournal8793738