The number of receptors for factor VII correlates with the ability of cultured cells to initiate coagulation

Abstract Previously, we showed that cells derived from nonvascular tissues initiate clotting primarily by markedly increasing the activity of coagulation factor VII. Cells derived from vascular tissue do not normally exhibit this property (tissue factor activity). In this study, we have characterized the relationship between the tissue factor activity of cultured cells derived from normal tissues and the number of receptors they possess for coagulation factor VII. Only cultured nonvascular cells expressed tissue factor activity or possessed receptors for 125I-factor VII. Fetal lung cells, the nonvascular tissue with the largest amount of procoagulant and tissue factor activity, possessed the most receptors for 125I-factor VII (880,000/cell). Bovine corneal endothelial cells, the nonvascular tissue possessing the fewest number of receptors (2,400/cell), had the least amount of procoagulant or tissue factor activity. The affinity of nonvascular cells for 125I- factor VII varied for the cells studied (Kd congruent to 1.3–90 X 10(- 10) M). Vascular cells expressed no tissue factor activity, nor did they bind 125I-factor VII. 125I-factor VII and unlabeled factor VII bound to cells had identical procoagulant activities. These results indicate that the ability of cultured cells to initiate coagulation may be regulated in part by the number of receptors they possess for factor VII.

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The number of receptors for factor VII correlates with the ability of cultured cells to initiate coagulation

Blood ◽

10.1182/blood.v63.2.434.bloodjournal632434 ◽

1984 ◽

Vol 63 (2) ◽

pp. 434-438 ◽

Cited By ~ 1

Author(s):

GM Rodgers ◽

GJ Jr Broze ◽

MA Shuman

Keyword(s):

Tissue Factor ◽

Vascular Tissue ◽

Cultured Cells ◽

Coagulation Factor ◽

Fetal Lung ◽

Factor Vii ◽

Factor Activity ◽

Coagulation Factor Vii ◽

Normal Tissues ◽

Tissue Factor Activity

Previously, we showed that cells derived from nonvascular tissues initiate clotting primarily by markedly increasing the activity of coagulation factor VII. Cells derived from vascular tissue do not normally exhibit this property (tissue factor activity). In this study, we have characterized the relationship between the tissue factor activity of cultured cells derived from normal tissues and the number of receptors they possess for coagulation factor VII. Only cultured nonvascular cells expressed tissue factor activity or possessed receptors for 125I-factor VII. Fetal lung cells, the nonvascular tissue with the largest amount of procoagulant and tissue factor activity, possessed the most receptors for 125I-factor VII (880,000/cell). Bovine corneal endothelial cells, the nonvascular tissue possessing the fewest number of receptors (2,400/cell), had the least amount of procoagulant or tissue factor activity. The affinity of nonvascular cells for 125I- factor VII varied for the cells studied (Kd congruent to 1.3–90 X 10(- 10) M). Vascular cells expressed no tissue factor activity, nor did they bind 125I-factor VII. 125I-factor VII and unlabeled factor VII bound to cells had identical procoagulant activities. These results indicate that the ability of cultured cells to initiate coagulation may be regulated in part by the number of receptors they possess for factor VII.

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Circulating Tissue Factor Procoagulant Activity and Thrombin Generation in Patients with Type 2 Diabetes: Effects of Insulin and Glucose

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-0933 ◽

2007 ◽

Vol 92 (11) ◽

pp. 4352-4358 ◽

Cited By ~ 83

Author(s):

Guenther Boden ◽

Vijender R. Vaidyula ◽

Carol Homko ◽

Peter Cheung ◽

A. Koneti Rao

Keyword(s):

Type 2 Diabetes ◽

Tissue Factor ◽

Blood Coagulation ◽

Coagulation Factor ◽

Procoagulant Activity ◽

Factor Vii ◽

Coagulation Factor Vii ◽

Glucose Levels ◽

Study Protocols

Abstract Context: Type 2 diabetes mellitus (T2DM) is a hypercoagulable state. Tissue factor (TF) is the principal initiator of blood coagulation. Objective: Our objective was to examine the effects of hyperglycemia and hyperinsulinemia on the TF pathway of blood coagulation in T2DM. Design: Three study protocols were used: 1) acute correction of hyperglycemia (with iv insulin) followed by 24 h of euglycemia, 2) 24 h of selective hyperinsulinemia, and 3) 24 h of combined hyperinsulinemia and hyperglycemia. Setting: The study took place at a clinical research center. Study Participants: Participants included 18 T2DM patients and 22 nondiabetic controls. Results: Basal TF-procoagulant activity (TF-PCA), monocyte TF mRNA, plasma coagulation factor VII (FVIIc), and thrombin-anti-thrombin complexes were higher in T2DM than in nondiabetic controls, indicating a chronic procoagulant state. Acutely normalizing hyperglycemia over 2–4 h resulted in a small (∼7%) but significant decline in TF-PCA with no further decline over 24 h. Raising insulin levels alone raised TF-PCA by 30%, whereas raising insulin and glucose levels together increased TF-PCA (by 80%), thrombin-anti-thrombin complexes, and prothrombin fragment 1.2. Plasma FVIIa and FVIIc declined with increases in TF-PCA. Conclusion: We conclude that the combination of hyperglycemia and hyperinsulinemia, common in poorly controlled patients with T2DM, contributes to a procoagulant state that may predispose these patients to acute cardiovascular events.

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Evidence for the presence of tissue factor activity on subendothelium

Blood ◽

10.1182/blood.v73.4.968.bloodjournal734968 ◽

1989 ◽

Vol 73 (4) ◽

pp. 968-975

Author(s):

HJ Weiss ◽

VT Turitto ◽

HR Baumgartner ◽

Y Nemerson ◽

T Hoffmann

Keyword(s):

Tissue Factor ◽

Umbilical Artery ◽

Factor Viia ◽

Rabbit Aorta ◽

Coagulation Factors ◽

Factor Vii ◽

Factor X ◽

Factor Activity ◽

Fibrin Deposition ◽

Tissue Factor Activity

By a variety of methods, tissue factor activity was demonstrated in the subendothelium of rabbit aorta and human umbilical artery. In one method, everted segments of de-endothelialized vessels were mounted in an annular perfusion chamber and the subendothelial surface was exposed to nonanticoagulated human blood under controlled flow. Procoagulant activity was assessed by measuring fibrin deposition on subendothelium and fibrinopeptide A (FPA) levels in post chamber blood. Both fibrin deposition and FPA were decreased with rabbit vessel segments exposed (at a shear rate of 650 seconds-1) to blood from patients with factor VII deficiency and with umbilical artery segments (at shear rates of 90 to 180 seconds-1) that had been pretreated with a monoclonal antibody to human tissue factor. In a second method, everted umbilical artery segments were mounted on a stir bar and the subendothelial surface was exposed, with stirring, to plasma or purified coagulation factors. The capacity of the surface to clot plasma on addition of calcium was inhibited by the antibody to tissue factor. The surface also activated purified 3H-factor X in the presence of factor VIIa, but not in its absence, and this surface property was almost entirely eliminated by pretreating the vessel segments with antitissue factor. Tissue factor activity in subendothelium could play a role in both the arrest of bleeding and in promoting the formation of thrombi at sites of vascular injury.

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Tissue factor and factor VII messenger RNAs in human alveolar macrophages: effects of breathing ozone

Blood ◽

10.1182/blood.v75.1.122.122 ◽

1990 ◽

Vol 75 (1) ◽

pp. 122-127 ◽

Cited By ~ 18

Author(s):

MP McGee ◽

R Devlin ◽

G Saluta ◽

H Koren

Keyword(s):

Alveolar Macrophage ◽

Tissue Factor ◽

Alveolar Macrophages ◽

Factor Vii ◽

Fibrinopeptide A ◽

Factor Activity ◽

Tissue Factor Activity ◽

Mrna Concentration ◽

Human Alveolar Macrophages

Abstract This study was performed to determine if genes for tissue factor and factor VII proteins are expressed and regulated in vivo in lung macrophages during inflammation. Human alveolar macrophages and alveolar fluids were obtained 18 hours after healthy male adults were exposed, for 2 hours during intermittent exercise, to either air or air with 0.4 ppm ozone, added as a model toxic respiratory agent. Messenger RNA (mRNA) for both tissue factor and factor VII were demonstrated in macrophages isolated after subjects were exposed to unpolluted control air. With the same subjects examined after breathing ozone, the following changes were observed: tissue factor mRNA concentration in macrophages increased 2.6 +/- 0.47-fold. Factor VII mRNA concentration was reduced 0.64 +/- 0.24-fold. Total numbers of macrophages recovered did not change significantly. Ratios of nuclear:cytoplasmic areas of cytocentrifuged macrophages were augmented by 24.8% +/- 3%, giving morphometric evidence that immature cell forms increased in the population. In the lavage, tissue factor activity was increased 2.1 +/- 0.3-fold, while amounts of lipid phosphorous, which estimate total membrane lipids, and estimated volumes of alveolar fluid were not significantly changed. Factor VII activity and fibrinopeptide A levels in lavage were increased approximately twofold. These results using rapidly isolated, noncultured cells indicate that tissue factor and factor VII mRNA are synthesized in the alveolar macrophage population in vivo. In addition, evidence was found that as a result of breathing ozone, a shift in alveolar macrophage maturity occurred in association with tissue factor mRNA, tissue factor activity, and factor VII activity increases, and with formation of fibrinopeptide A in alveolar fluids.

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