Long-term incubation with IL-4 and IL-10 oppositely modifies procoagulant activity of monocytes and modulates the surface expression of tissue factor and tissue factor pathway inhibitor

2005 ◽  
Vol 131 (3) ◽  
pp. 356-365 ◽  
Author(s):  
Jerome Paysant ◽  
Claudine Soria ◽  
Pascale Cornillet-Lefebvre ◽  
Philippe Nguyen ◽  
Bernard Lenormand ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Surface Expression ◽  
Procoagulant Activity ◽  
Tissue Factor Pathway

Regulation of monocyte procoagulant activity in acute myocardial infarction: role of tissue factor and tissue factor pathway inhibitor-1

Blood ◽  
2001 ◽  
Vol 97 (12) ◽  
pp. 3721-3726 ◽  
Author(s):  
Ilka Ott ◽  
Martin Andrassy ◽  
Dominik Zieglgänsberger ◽  
Stefanie Geith ◽  
Albert Schömig ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Polyclonal Antibodies ◽  
Venous Blood ◽  
Surface Expression ◽  
Procoagulant Activity ◽  
Control Group ◽  
Tissue Factor Pathway

In acute myocardial infarction (AMI), monocyte procoagulant activity is increased and may contribute to the risk for recurrence and other thrombotic events. This study sought to investigate the role tissue factor (TF) and tissue factor pathway inhibitor-1 (TFPI-1) in the regulation of monocyte procoagulant activity in AMI. Serial venous blood samples were obtained from 40 patients with AMI undergoing revascularization by stent placement. Twenty patients with elective stenting for stable angina served as control subjects. TF proteolytic activity was measured with spectrozyme factor Xa (FXa), TF and TFPI-1 surface expression on monocytes by flow cytometry, RNA expression in whole blood by reverse transcription–polymerase chain reaction, and concentrations of plasma prothrombin fragments F1 + 2 by immunoassay. Forty-eight hours after AMI, an increase was found in TF RNA, followed by an increase in TF surface expression by 24% ± 4% and in plasma concentration of F1 + 2 by 103% ± 17% (P < .05). These changes could not be attributed to the intervention because they did not occur in the control group. TFPI-1 RNA and binding to the monocyte surface remained unchanged. FXa generation by monocytes of patients with AMI increased 53.6% ± 9% in the presence of polyclonal antibodies to TFPI-1, indicating that cell-associated TFPI-1 inhibits monocyte TF activity. The increased monocyte procoagulant activity in AMI was caused by an up-regulation of TF that was partially inhibited by surface-bound TFPI-1. Anticoagulant therapy by direct inhibition of TF activity may, thus, be particularly effective in AMI.

Procoagulant Activity of Laminaria Japonica Derived Fucoidan (BAX513) Depends on the Interaction with the C-Terminus of Tissue Factor Pathway Inhibitor

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4417-4417 ◽  
Author(s):  
Michael Palige ◽  
Christoph Redl ◽  
Sabine Knappe ◽  
Hartmut J. Ehrlich ◽  
Michael Dockal ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Mechanism Of Action ◽  
Thrombin Generation ◽  
Tissue Factor Pathway Inhibitor ◽  
Laminaria Japonica ◽  
Full Length ◽  
Procoagulant Activity ◽  
C Terminus ◽  
Tissue Factor Pathway ◽  
Dose Dependent

Abstract Abstract 4417 BAX513, a fucoidan derived from the brown seaweed Laminaria japonica, and other non-anticoagulant sulfated polysaccharides (NASPs) improve coagulation in hemophilic blood and plasma. Fucoidans are heterogeneous, polysulfated molecules with procoagulant activities in a wide concentration range. Tissue factor pathway inhibitor (TFPI) has been described as a potential target for the procoagulant activity of NASPs (Liu et al. Thromb Haemost 2006; 95:68). In the current study, we investigated the interaction of BAX513 with TFPI proteins to gain a detailed understanding of the mechanism of action of BAX513. We used calibrated automated thrombography to monitor the activity of BAX513 in normal, FX and TFPI-deficient plasma. TFPI plasma levels were varied by the addition of truncated TFPI (TFPI1-160) and TFPI-domain specific antibodies. Initiating thrombin generation by addition of FXa to plasma deficient in both, FX and FVIII-showed a BAX513-dose dependent increase of thrombin generation, which was completely abolished when TFPI-specific polyclonal antibodies were present. Furthermore, when full-length TFPI was inhibited in plasma and instead supplemented with increasing amounts of TFPI 1–160, BAX513 did not show any activity. The data are further supported by surface plasmon resonance experiments (BiaCore) exploring the BAX513-TFPI interaction. A high affinity interaction was only observed for BAX513 with full-length TFPI but not for BAX513 with TFPI1-160. Our findings support a mechanism of action in which BAX513 acts as a potent dose-dependent TFPI antagonist that requires the highly charged C-terminus of TFPI to unfold its full potential. Understanding the mechanism of action of BAX513 supports the development of BAX513 as a promising new therapeutic for hemophiliacs and FVIII-inhibitor patients. Disclosures: Palige: Baxter Innovations GmbH: Employment. Redl:Baxter Innovations GmbH: Employment. Knappe:Baxter Innovations GmbH: Employment. Ehrlich:Baxter Innovations GmbH: Employment. Dockal:Baxter Innovations GmbH: Employment. Scheiflinger:Baxter Innovations GmbH: Employment.

Tissue factor/tissue factor pathway inhibitor system and long-term prognosis after acute myocardial infarction

2001 ◽  
Vol 78 (2) ◽  
pp. 115-119 ◽  
Author(s):  
Vanessa Roldán ◽  
Francisco Marín ◽  
Pascual Fernández ◽  
Juan Luján ◽  
Juan G. Martínez ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Inhibitor System ◽  
Tissue Factor Pathway ◽  
Long Term Prognosis

Tissue Factor Reduction and Tissue Factor Pathway Inhibitor Release after Heparin Administration

1999 ◽  
Vol 81 (04) ◽  
pp. 589-593 ◽  
Author(s):  
A. M. Gori ◽  
G. Pepe ◽  
M. Attanasio ◽  
M. Falciani ◽  
R. Abbate ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Plasma Levels ◽  
Tissue Factor Pathway Inhibitor ◽  
Day Treatment ◽  
Procoagulant Activity ◽  
Cytokine Gene Expression ◽  
Heparin Administration ◽  
Tissue Factor Pathway

SummaryElevated plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) and large amounts of monocyte procoagulant activity (PCA) have been documented in unstable angina (UA) patients. In in vitro experiments heparin is able to blunt monocyte TF production by inhibiting TF and cytokine gene expression by stimulated cells and after in vivo administration it reduces adverse ischemic outcomes in UA patients. TF and TFPI plasma levels and monocyte PCA have been investigated in 28 refractory UA patients before and during anticoagulant subcutaneous heparin administration (thrice daily weight- and PTT-adjusted for 3 days) followed by 5000 IU × 3 for 5 days. After 2-day treatment, immediately prior to the heparin injection, TF and TFPI plasma levels [(median and range): 239 pg/ml, 130-385 pg/ ml and 120 ng/ml, 80-287 ng/ml] were lower in comparison to baseline samples (254.5 pg/ml, 134.6-380 pg/ml and 135.5 ng/ml, 74-306 ng/ml). Four h after the heparin injection TF furtherly decreased (176.5 pg/ml, 87.5-321 pg/ml; -32.5%, p<0.001) and TFPI increased (240.5 ng/ml, 140-450 ng/ml; +67%, p<0.0001).After 7-day treatment, before the injection of heparin, TF and TFPI plasma levels (200 pg/ml, 128-325 pg/ml and 115 ng/ml, 70-252 ng/ml) significantly decreased (p<0.05) in comparison to the pre-treatment values. On the morning of the 8th day, 4 h after the injection of heparin TF plasma levels and monocytes PCA significantly decreased (156.5 pg/ml, 74-259 pg/ml and from 180 U/105 monocytes, 109-582 U/105 monocytes to 86.1 U/105 monocytes, 28-320 U/105 monocytes; - 38% and -55% respectively) and TFPI increased (235.6 ng/ml, 152-423 ng/ ml; +70%, p<0.001). In conclusion, heparin treatment is associated with a decrease of high TF plasma levels and monocyte procoagulant activity in UA patients. These actions of heparin may play a role in determining the antithrombotic and antiinflammatory properties of this drug.

Procoagulant activity in bronchoalveolar fluids: No relationship with tissue factor pathway inhibitor activity

1992 ◽  
Vol 65 (4-5) ◽  
pp. 507-518 ◽  
Author(s):  
Philippe de Moerloose ◽  
Edoardo De Benedetti ◽  
Laurent Nicod ◽  
Catherine Vifian ◽  
Guido Reber
Keyword(s):  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Procoagulant Activity ◽  
Inhibitor Activity ◽  
Tissue Factor Pathway

scholarly journals Intra-alveolar tissue factor pathway inhibitor is not sufficient to block tissue factor procoagulant activity

2008 ◽  
Vol 294 (5) ◽  
pp. L874-L881 ◽  
Author(s):  
Julie A. Bastarache ◽  
Ling Wang ◽  
Zhengming Wang ◽  
Kurt H. Albertine ◽  
Michael A. Matthay ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Pulmonary Edema ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Distress Syndrome ◽  
Alveolar Epithelium ◽  
Procoagulant Activity ◽  
Fibrin Deposition ◽  
Edema Fluid ◽  
Tissue Factor Pathway

The alveolar compartment in acute lung injury contains high levels of tissue factor (TF) procoagulant activity favoring fibrin deposition. We previously reported that the alveolar epithelium can release TF procoagulant activity in response to a proinflammatory stimulus. To test the hypothesis that the alveolar epithelium further modulates intra-alveolar fibrin deposition through secretion of an endogenous inhibitor to TF, tissue factor pathway inhibitor (TFPI), we measured TFPI levels in edema fluid (EF) from patients with acute respiratory distress syndrome. To determine whether the alveolar epithelium can release TFPI, both full-length TFPI and truncated TFPI were measured (ELISA) in pulmonary edema fluid from patients with acute respiratory distress syndrome (ARDS) and a control group of patients with hydrostatic pulmonary edema (HYDRO). TFPI protein was also measured in conditioned media (CM) and cell lysates (CL) from human alveolar epithelial cells (A549) after exposure to cytomix (TNF-α, IL-1β, IFN-γ). TFPI protein levels were higher in pulmonary edema fluid from patients with ARDS vs. HYDRO. TFPI protein was increased in CM and did not change in CL after cytomix treatment; TFPI mRNA levels (RT-PCR) did not change. Despite the high levels of TFPI, both the EF and CM retained significant TF procoagulant activity as measured by plasma recalcification time. The majority of intra-alveolar TFPI was in a truncated, inactive form, whereas the majority of TFPI released from cells was full length, suggesting different mechanisms of inactivation. In summary, the alveolar epithelium releases TFPI in response to an inflammatory stimulus but does not increase TFPI gene transcription or protein production. Levels of intra-alveolar TFPI in ARDS are not sufficient to block intra-alveolar TF procoagulant activity due to truncation and inactivation of intra-alveolar TFPI.

scholarly journals Active tissue factor pathway inhibitor is expressed on the surface of coated platelets

Blood ◽  
2006 ◽  
Vol 109 (5) ◽  
pp. 1931-1937 ◽  
Author(s):  
Susan A. Maroney ◽  
Sandra L. Haberichter ◽  
Paul Friese ◽  
Maureen L. Collins ◽  
Josephine P. Ferrel ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Blood Clot ◽  
Surface Expression ◽  
Receptor Activation ◽  
Optimal Location ◽  
Thrombin Receptor ◽  
Platelet Surface ◽  
Tissue Factor Pathway ◽  
Dual Agonist

Abstract The incorporation of blood-borne forms of tissue factor (TF) into a growing blood clot is necessary for normal fibrin generation and stabilization of the blood clot. Tissue factor pathway inhibitor (TFPI) is the primary physiologic inhibitor of tissue factor and is present within platelets. Expression of TFPI on the platelet surface may be the optimal location for it to abrogate blood-borne TF activity that incorporates within the blood clot, balancing the need for adequate hemostasis while preventing development of occlusive thrombosis. TFPI is produced by megakaryocytes but is not expressed on the platelet surface. Activation of platelets with thrombin receptor activation peptide does not cause release or surface expression of TFPI, demonstrating that TFPI is not stored within platelet α granules. TFPI is expressed on the platelet surface following dual-agonist activation with convulxin plus thrombin to produce coated platelets. In association with its expression on the surface of coated platelets TFPI is also released in microvesicles or as a soluble protein.

Sign in / Sign up

Export Citation Format

Share Document