Abstract
Background. Activated factor X (FXa) is involved in hemostasis, thrombogenesis, inflammation,
and cellular immune response. Tissue factor (TF) is an initiator of blood coagulation.
We investigated whether FXa induces TF expression in human peripheral monocytes and
whether treatment with FXa inhibitor reduces TF expression in an experimental model
of rat endotoxemia. Methods. Human peripheral mononuclear cells were used to determine TF expression induced by
FXa. Experimental rat endotoxemia was induced by intravenous bolus injection of lipopolysaccharide
(LPS). A specific FXa inhibitor, DX-9065a, was administered subcutaneously immediately
after LPS injection. Results. FXa induced TF expression in monocytes without intervention of thrombin and the expression
was suppressed by FXa inhibitor. In the experimental model of rat endotoxemia, TF
and TF mRNA expression levels in the liver were reduced by DX-9065a. Moreover, administration
of DX-9065a suppressed the rise in plasma concentrations of thrombin-antithrombin
III complex (TAT) and monocyte chemoattractant protein-1 (MCP-1). Conclusions. Our results indicated that FXa can induce TF expression in human peripheral monocytes
and that inhibition of FXa reduces TF expression in the liver of rat endotoxemia.
These results suggest that FXa is an important factor for TF expression in sepsis.
(Surgery 2001;130:809-18.)
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References
- The coagulation cascade: initiation, maintenance, and regulation.Biochemistry. 1991; 30: 10363-10370
- Effector cell protease receptor-1 is a vascular receptor for coagulation factor Xa.J Biol Chem. 1996; 271: 28407-28413
- Human umbilical vein endothelial cells express high affinity receptors for factor Xa.J Cell Physiol. 1997; 172: 36-43
- Coagulation factor Xa stimulates platelet-derived growth factor release and mitogenesis in cultured vascular smooth muscle cells of rat.J Clin Invest. 1996; 98: 1493-1501
- Factor Xa as an interface between coagulation and inflammation. Molecular mimicry of factor Xa association with effector cell protease receptor-1 induces acute inflammation in vivo.J Clin Invest. 1997; 99: 2446-2451
- Activation of human vascular endothelial cells by factor Xa: effect of specific inhibitors.Biochem Pharmacol. 1999; 57: 603-610
- Factor Xa induces cytokine production and expression of adhesion molecules by human umbilical vein endothelial cells.J Immunol. 1998; 161: 4318-4324
- Hypotension and inflammatory cytokine gene expression triggered by factor Xa-nitric oxide signaling.Proc Natl Acad Sci U S A. 1998; 95: 4738-4742
- Tissue factor and hemostasis.Blood. 1988; 71: 1-8
- Possible role of platelet-activating factor in the in vivo expression of tissue factor in neutrophils.J Surg Res. 1998; 80: 149-155
- Lipopolysaccharide induction of tissue factor in THP-1 cells involves Jun protein phosphorylation and nuclear factor κB nuclear translocation.J Biol Chem. 1999; 274: 376-383
- Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis.Am J Pathol. 1989; 134: 1087-1097
- Regulation of tissue factor gene expression in the monocyte procoagulant response to endotoxin.Mol Cell Biol. 1989; 9: 2752-2755
- Disseminated intravascular coagulation in rabbits induced by administration of endotoxin or tissue factor: effect of anti-tissue factor antibodies and measurement of plasma extrinsic pathway inhibitor activity.Blood. 1990; 75: 1481-1489
- Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody.Circ Shock. 1991; 33: 127-134
- Prevention of endotoxin-induced mortality by antitissue factor immunization.Arch Surg. 1996; 131: 1273-1278
- Macrophages and neutrophils infiltrating into the liver are responsible for tissue factor expression in a rabbit model of acute obstructive cholangitis.Thromb Haemost. 1996; 75: 791-795
- Neutrophils express tissue factor in a monkey model of sepsis.Surgery. 2000; 127: 209-216
- Effects of DX- 9065a, an orally active, newly synthesized and specific inhibitor of factor Xa, against experimental disseminated intravascular coagulation in rats.Thromb Haemost. 1994; 72: 393-396
- Antithrombotic and hemorrhagic effects of DX-9065a, a direct and selective factor Xa inhibitor: comparison with a direct thrombin inhibitor and antithrombin III-dependent anticoagulants.Thromb Haemost. 1997; 78: 1366-1371
- Inhibition of thrombin generation in plasma by inhibitors of factor Xa.Thromb Haemost. 1997; 78: 1215-1220
- Effects of a factor Xa inhibitor, DX-9065a, in a novel rabbit model of venous thrombosis.Basic Res Cardiol. 1999; 94: 15-22
- A specific inhibitor of factor Xa, DX-9065a, exerts effective protection against experimental tumor induced disseminated intravascular coagulation in rats.Thromb Res. 1999; 96: 135-143
- A synthetic selective inhibitor of factor Xa, DX-9065a, reduces monocyte chemoattractant protein-1 expression after ischemia-reperfusion injury in rat liver.Dig Dis Sci. 1999; 44: 2568-2576
- Inactivation of factor Xa by the synthetic inhibitor DX-9065a causes strong anticoagulant and antiplatelet actions in human blood.Blood Coagul Fibrinolysis. 1999; 10: 495-501
- Thrombin regulates tissue factor and thrombomodulin mRNA levels and activities in human saphenous vein endothelial cells by distinct mechanisms.J Biol Chem. 1993; 268: 421-429
- Thrombin activates nuclear factor-κB and potentiates endothelial cell activation by TNF.J Immunol. 1997; 159: 5620-5628
- The importance of platelets in the expression of monocyte tissue factor antigen measured by a new whole blood flow cytometric assay.Thromb Haemost. 1996; 75: 87-95
- A novel microtiter plate assay for the quantitation of procoagulant activity on adherent monocytes, macrophage and endothelial cells.Thromb Res. 1989; 53: 339-346
- Measurement of tissue factor messenger RNA levels in human endothelial cells by a quantitative RT-PCR assay.Thromb Haemost. 1994; 71: 208-213
- Expression of tissue factor in hepatic ischemic-reperfusion injury of the rat.Transplantation. 1998; 66: 708-716
- Angiotensin II increases plasminogen activator inhibitor-1 and tissue factor mRNA expression without changing that of tissue type plasminogen activator or tissue factor pathway inhibitor in cultured rat aortic endothelial cells.Thromb Haemost. 1997; 77: 1189-1195
- Tissue factor is induced by monocyte chemoattractant protein-1 in human aortic smooth muscle and THP-1 cells.J Biol Chem. 1997; 272: 28568-28573
- Permeability enhancing and chemotactic activities of lower molecular weight degradation products of human fibrinogen.Thromb Haemost. 1981; 45: 90-94
- Effects of fibrinogen derivatives upon the inflammatory response. Studies with human fibrinopeptide B.J Clin Invest. 1986; 77: 1014-1019
- The antithrombotic effect of synthetic low molecular weight human factor Xa inhibitor, DX-9065a, on He-Ne laser-induced thrombosis in rat mesenteric microvessels.Thromb Res. 1997; 85: 45-51
- Priming for enhanced alveolar fibrin deposition after hemorrhagic shock: role of tumor necrosis factor.Am J Respir Cell Mol Biol. 2000; 22: 412-421
- Blood-borne tissue factor: another view of thrombosis.Proc Natl Acad Sci U S A. 1999; 96: 2311-2315
- Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor.Blood. 2000; 96: 170-175
Article info
Publication history
Accepted:
April 9,
2001
Footnotes
*Reprint requests: Kohji Okamoto, MD, Department of Surgery I, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
Identification
Copyright
© 2001 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
