Local Anesthetics Inhibit Tissue Factor Expression in Activated Monocytes via Inhibition of Tissue Factor mRNA Synthesis

2010 ◽  
Vol 17 (6) ◽  
pp. E4-E9 ◽  
Author(s):  
Ji-Eun Kim ◽  
Ki Jun Kim ◽  
Wonsik Ahn ◽  
Kyou-Sup Han ◽  
Hyun Kyung Kim
Keyword(s):  
Tissue Factor ◽  
Local Anesthetics ◽  
Messenger Rna ◽  
Mrna Level ◽  
Dependent Manner ◽  
Tissue Factor Expression ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Factor Expression ◽  
Activated Monocytes

Local anesthetics have been reported to have anticoagulant properties, but the mechanisms responsible for this action are poorly understood. Here, we evaluated the in vitro effects of 3 local anesthetics—lidocaine, ropivacaine, and bupivacaine—on the tissue factor expression by monocytes. Monocytes from peripheral blood were stimulated with lipopolysaccharide (LPS) in the presence or absence of local anesthetics. All 3 local anesthetics inhibited the expression of tissue factor antigen and tissue factor activity in LPS-stimulated monocytes in a dose- and time-dependent manner and reduced tissue factor messenger RNA (mRNA) expression in endothelial cells and a monocytic cell line. None of the 3 drugs induced apoptosis or affected the viability of monocytes. Our findings that local anesthetics inhibited the tissue factor induction in activated monocytes by inhibiting tissue factor mRNA level may demonstrate the feasibility of using local anesthetics in hypercoagulable and inflammatory conditions.

Adenosine Inhibits Tissue Factor Expression by LPS-stimulated Human Monocytes: Involvement of the A3 Adenosine Receptor

2002 ◽  
Vol 88 (07) ◽  
pp. 123-130 ◽  
Author(s):  
Matthieu Broussas ◽  
Pascale Cornillet-Lefèbvre ◽  
Gérard Potron ◽  
Philippe Nguyên
Keyword(s):  
Tissue Factor ◽  
Rank Order ◽  
Mrna Level ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Extrinsic Pathway ◽  
A3 Adenosine Receptor ◽  
Factor Expression ◽  
Cardioprotective Effects ◽  
Dose Dependent

SummaryTissue Factor (TF), an integral membrane glycoprotein that initiates the extrinsic pathway of blood coagulation, is thought to play a major part in coronary acute events. Adenosine, an endogenous nucleoside produced by the degradation of intracellular adenosine triphosphate, has been shown to exert many cardioprotective effects via an inhibition of platelets and neutrophils. This study was conducted to determine whether adenosine (ADO) could modulate the expression of TF by human monocytes. We found that ADO inhibited TF antigen and activity on endotoxin-stimulated monocytes in a dose-dependent manner. The mechanism was at least pre-translational since ADO caused a change in the TF mRNA level. Using ADO receptor-specific analogs, we showed that highly selective A3 agonist N6-(3-iodobenzyl)-adenosine-5’-N’-methyluronamide (IB-MECA) inhibited LPSinduced TF activity expression more potently than A1 agonist R-phenylisopropyladenosine (R-PIA) and A2 agonist CGS 2180. Furthermore, A1/A3 antagonist, xanthine amine congener (XAC) blocked the effect of ADO whereas A2a, A2b and A1 antagonists were ineffective. In addition, we observed that ADO agonists inhibited monocyte TF expression in LPS-stimulated whole blood. The rank order of agonist potency suggested that A2 and A3 receptors might be involved (2-Cado > CGS = IB-MECA > R-PIA). This was supported by the fact that A2 and A3 antagonists reversed the action of 2-Cado. We conclude that TF inhibition by ADO on human purified monocytes involved A3 receptors.

TGF-β1 Induces Tissue Factor Expression in Human Lung Fibroblasts in a PI3K/JNK/Akt-Dependent and AP-1–Dependent Manner

2012 ◽  
Vol 47 (5) ◽  
pp. 614-627 ◽  
Author(s):  
Malgorzata Wygrecka ◽  
Dariusz Zakrzewicz ◽  
Brigitte Taborski ◽  
Miroslava Didiasova ◽  
Grazyna Kwapiszewska ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Dependent Manner ◽  
Tissue Factor Expression ◽  
Human Lung Fibroblasts ◽  
Factor Expression ◽  
Tgf Β1

scholarly journals Activated protein C suppresses tissue factor expression on U937 cells in the endothelial protein C receptor-dependent manner

FEBS Letters ◽  
2000 ◽  
Vol 477 (3) ◽  
pp. 208-212 ◽  
Author(s):  
Fang Shu ◽  
Hiroshi Kobayashi ◽  
Kenji Fukudome ◽  
Naoko Tsuneyoshi ◽  
Masao Kimoto ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Protein C ◽  
Activated Protein C ◽  
Dependent Manner ◽  
U937 Cells ◽  
Tissue Factor Expression ◽  
Endothelial Protein C Receptor ◽  
Factor Expression

Induction of Tissue Factor Expression in Whole Blood: Lack of Evidence for the Presence of Tissue Factor Expression in Granulocytes

2000 ◽  
Vol 83 (06) ◽  
pp. 861-867 ◽  
Author(s):  
Bjarne Østerud ◽  
Jan Olsen ◽  
L. Vijaya Rao
Keyword(s):  
Tumor Necrosis Factor ◽  
Tissue Factor ◽  
Whole Blood ◽  
Blood Cells ◽  
Tumor Necrosis ◽  
Platelet Rich Plasma ◽  
Tissue Factor Expression ◽  
Factor Expression ◽  
Activated Monocytes ◽  
Necrosis Factor

SummaryThe present investigation was undertaken to explore the effect of platelets, tumor necrosis factor (TNF) and phorbel ester [phorbol 12-myristate 13-acetate (PMA)] on lipopolysaccharide (LPS)-induced tissue factor (TF) activity and TF antigen by using Western blot and ELISA-techniques. LPS was found to induce correlating levels of TF antigen and the activity in monocytes. TNF and PMA, when used alone, failed to induce TF activity and the antigen in monocytes, but enhanced the LPS-induced TF activity and the antigen by 2 to 3-fold. Addition of platelet rich plasma to isolated blood cells enhanced the LPS-induced TF activity but not the antigen levels in monocytes. In contrast to whole platelets, platelet lysates enhanced both LPS-induced TF activity and the antigen. Granulocytes isolated from heparinized plasma incubated for 2 or 24 h with LPS alone or together with PMA, failed to generate TF antigen or the activity. Although granulocyte preparations isolated from whole blood that was incubated for 24 h with LPS and PMA apparently possessed a significant amount of TF activity and the antigen, this could be accounted for by trace levels of contaminating monocytes. Upregulation of LPS-induced TF activity but not the antigen by platelets in the presence of granulocytes suggests that the increased TF activity could be the result of PS enrichment of monocytes by fusion or platelets with activated monocytes.

scholarly journals Tissue Factor Expression in Bovine Endothelial Cells Induced by Pasteurella haemolytica Lipopolysaccharide and Interleukin-1

1994 ◽  
Vol 31 (1) ◽  
pp. 55-60 ◽  
Author(s):  
M. A. Breider ◽  
Z. Yang
Keyword(s):  
Endothelial Cells ◽  
Tissue Factor ◽  
Interleukin 1 ◽  
Cellular Tissue ◽  
Pasteurella Haemolytica ◽  
Dependent Manner ◽  
Tissue Factor Expression ◽  
Vascular Thrombosis ◽  
Factor Expression

Pasteurella haemolytica in cattle produces fibrinohemorrhagic pleuropneumonia characterized by extensive pulmonary microvascular thrombosis and parenchymal necrosis. The purpose of this in vitro study was to determine if P. haemolytica lipopolysaccharide (LPS) promotes vascular thrombosis by inducing a procoagulant state in vascular endothelial cells. After treatment of confluent monolayers of bovine pulmonary artery endothelial cells with various concentrations of either P. haemolytica LPS or Escherichia coli LPS, the procoagulant activity of the endothelial cells was determined using a chromogenic assay dependent on cellular tissue factor expression. The LPS treatment induced significant increases in cellular tissue factor expression in a LPS concentration- and time-dependent manner. Highest levels of tissue factor were present at 22 hours after treatment, although high LPS concentrations induced moderate tissue factor levels at 5 hours after treatment. Interleukin-1 also induced tissue factor expression in endothelial cells and enhanced the LPS-induced effects. This interleukin-1 effect could be diminished by concurrent use of an interleukin-1 receptor antagonist. These results demonstrate that LPS and cytokine promotion of a procoagulant state in endothelial cells occurs in vitro. Similar mechanisms may play a role in P. haemolytica-mediated pulmonary vascular thrombosis.

Induction of monocyte tissue factor expression by homocysteine: a possible mechanism for thrombosis

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 966-972 ◽  
Author(s):  
Annu Khajuria ◽  
Donald S. Houston
Keyword(s):  
Tissue Factor ◽  
Factor Vii ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Tissue Factor Expression ◽  
Thiol Compounds ◽  
Homocysteine Thiolactone ◽  
Cellular Targets ◽  
Factor Expression ◽  
Plausible Mechanism

Abstract Moderately elevated plasma homocysteine levels are an important independent risk factor for arterial and venous thrombosis and for atherosclerosis. Some investigators have proposed that homocysteine's effects result from oxidant injury to the vascular endothelium or from an alteration in endothelial function. However, homocysteine may have other cellular targets. We now report that homocysteine, at physiologically relevant concentrations, induces the expression of tissue factor by monocytes. In response to homocysteine, monocytes express procoagulant activity in a dose-dependent and a time-dependent manner. This activity is attributable to tissue factor because it was dependent on factor VII and blocked by anti-tissue factor antibodies. Tissue factor mRNA levels were also increased in monocytes after homocysteine treatment. The effect was found to be specific because analogues of homocysteine (homocystine and homocysteine thiolactone) did not mimic homocysteine's activity, nor did other thiol compounds (cysteine, 2-mercaptoethanol, dithiothreitol). On the other hand, methionine, the metabolic precursor of homocysteine, was active though less potent than homocysteine. Catalase and superoxide dismutase (scavengers of H2O2 and O2− Radicals, respectively) were unable to block the expression of tissue factor induced by homocysteine, as was a 5-fold excess of the reducing agent 2-mercaptoethanol. We conclude that the induction of tissue factor expression by circulating monocytes is a plausible mechanism by which homocysteine may induce thrombosis and that a nonspecific redox process is not involved.

scholarly journals Activated Monocytes Enhance Platelet-Driven Contraction of Blood Clots via Tissue Factor Expression

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Alina D. Peshkova ◽  
Giang Le Minh ◽  
Valerie Tutwiler ◽  
Izabella A. Andrianova ◽  
John W. Weisel ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Tissue Factor Expression ◽  
Blood Clots ◽  
Factor Expression ◽  
Activated Monocytes

Induction of monocyte tissue factor expression by homocysteine: a possible mechanism for thrombosis

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 966-972 ◽  
Author(s):  
Annu Khajuria ◽  
Donald S. Houston
Keyword(s):  
Tissue Factor ◽  
Factor Vii ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Tissue Factor Expression ◽  
Thiol Compounds ◽  
Homocysteine Thiolactone ◽  
Cellular Targets ◽  
Factor Expression ◽  
Plausible Mechanism

Moderately elevated plasma homocysteine levels are an important independent risk factor for arterial and venous thrombosis and for atherosclerosis. Some investigators have proposed that homocysteine's effects result from oxidant injury to the vascular endothelium or from an alteration in endothelial function. However, homocysteine may have other cellular targets. We now report that homocysteine, at physiologically relevant concentrations, induces the expression of tissue factor by monocytes. In response to homocysteine, monocytes express procoagulant activity in a dose-dependent and a time-dependent manner. This activity is attributable to tissue factor because it was dependent on factor VII and blocked by anti-tissue factor antibodies. Tissue factor mRNA levels were also increased in monocytes after homocysteine treatment. The effect was found to be specific because analogues of homocysteine (homocystine and homocysteine thiolactone) did not mimic homocysteine's activity, nor did other thiol compounds (cysteine, 2-mercaptoethanol, dithiothreitol). On the other hand, methionine, the metabolic precursor of homocysteine, was active though less potent than homocysteine. Catalase and superoxide dismutase (scavengers of H2O2 and O2− Radicals, respectively) were unable to block the expression of tissue factor induced by homocysteine, as was a 5-fold excess of the reducing agent 2-mercaptoethanol. We conclude that the induction of tissue factor expression by circulating monocytes is a plausible mechanism by which homocysteine may induce thrombosis and that a nonspecific redox process is not involved.

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