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

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.

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

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029610378500 ◽

2010 ◽

Vol 17 (6) ◽

pp. E4-E9 ◽

Cited By ~ 2

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.

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Endothelial Cell Function, Including Tissue Factor Expression, Under Flow Conditions

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642664 ◽

1995 ◽

Vol 74 (01) ◽

pp. 123-128 ◽

Cited By ~ 40

Author(s):

Eric F Grabowski ◽

Frances P Lam

Keyword(s):

Endothelial Cell ◽

Tissue Factor ◽

Cell Function ◽

Tissue Factor Expression ◽

Flow Conditions ◽

Endothelial Cell Function ◽

Factor Expression

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The Factor VIII Bypassing Activity of Prothrombin Complex Concentrates: The Roles of Factor VIla and of Endothelial Cell Tissue Factor

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646459 ◽

1991 ◽

Vol 66 (05) ◽

pp. 559-564 ◽

Cited By ~ 4

Author(s):

Jerome M Teitel

Keyword(s):

Factor Viii ◽

Tissue Factor ◽

Factor Viia ◽

Factor Xa ◽

Procoagulant Activity ◽

Tissue Factor Expression ◽

Prothrombin Complex Concentrates ◽

Cell Tissue ◽

Factor Expression ◽

Necrosis Factor

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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