Download PDF
Semin Thromb Hemost 2006; 32(1): 033-039
DOI: 10.1055/s-2006-933338
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Tissue Factor in Infection and Severe Inflammation

Marcel Levi1 , Tom van der Poll1 , 2 , Hugo ten Cate3
  • 1Department of Internal Medicine, Academic Hospital Maastricht, Maastricht, The Netherlands
  • 2Laboratory of Experimental Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  • 3Department of Internal Medicine, Academic Hospital Maastricht, Maastricht, The Netherlands
Further Information

Publication History

Publication Date:
15 February 2006 (online)

    Permissions and Reprints

ABSTRACT

In the pathogenesis of vascular disease, inflammation and coagulation play a pivotal role. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation not only leads to activation of coagulation, but coagulation also considerably affects inflammatory activity. Tissue factor (TF) plays an important role at the crossroad of coagulation and inflammation, as the principal initiator of coagulation and an important modulator of inflammation. Proinflammatory cytokines can induce TF expression on mononuclear cells and endothelial cells and thereby commence pathways that lead to thrombin generation. Simultaneously, TF may bind to cellular receptors, which may affect the production and release of inflammatory mediators. There is increasing experimental evidence that TF inhibition may have beneficial effects in disease states in which the combination of coagulation and inflammation plays a prominent role.

KEYWORDS

Coagulation - inflammation - infection - tissue factor - mononuclear cells - endothelium

REFERENCES

  • 1 Levi M, ten Cate H. Disseminated intravascular coagulation.  N Engl J Med. 1999;  341 586-592
    CrossrefPubMedSearch in Google Scholar
  • 2 Wheeler A P, Bernard G R. Treating patients with severe sepsis.  N Engl J Med. 1999;  340 207-214
    CrossrefPubMedSearch in Google Scholar
  • 3 Levi M. Current understanding of disseminated intravascular coagulation.  Br J Haematol. 2004;  124 567-576
    CrossrefPubMedSearch in Google Scholar
  • 4 Levi M, van der Poll T, Büller H R. Bidirectional relation between inflammation and coagulation.  Circulation. 2004;  109 2698-2704
    CrossrefPubMedSearch in Google Scholar
  • 5 Esmon C T. Introduction: are natural anticoagulants candidates for modulating the inflammatory response to endotoxin?.  Blood. 2000;  95 1113-1116
    PubMedSearch in Google Scholar
  • 6 Libby P, Aikawa M. Stabilization of atherosclerotic plaques: new mechanisms and clinical targets.  Nat Med. 2002;  8 1257-1262
    CrossrefPubMedSearch in Google Scholar
  • 7 Levi M, van der Poll T, ten Cate H, van Deventer S J. The cytokine-mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia.  Eur J Clin Invest. 1997;  27 3-9
    CrossrefPubMedSearch in Google Scholar
  • 8 Levi M, Keller T T, van Gorp E, ten Cate H. Infection and inflammation and the coagulation system.  Cardiovasc Res. 2003;  60 26-39
    CrossrefPubMedSearch in Google Scholar
  • 9 Esmon C T. The regulation of natural anticoagulant pathways.  Science. 1987;  235 1348-1352
    CrossrefPubMedSearch in Google Scholar
  • 10 Biemond B J, Levi M, ten Cate H et al.. Plasminogen activator and plasminogen activator inhibitor I release during experimental endotoxaemia in chimpanzees: effect of interventions in the cytokine and coagulation cascades.  Clin Sci. 1995;  88 587-594
    CrossrefPubMedSearch in Google Scholar
  • 11 Levi M, ten Cate H, Bauer K A et al.. Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees.  J Clin Invest. 1994;  93 114-120
    CrossrefPubMedSearch in Google Scholar
  • 12 Pixley R A, De La Cadena R A, Page J D et al.. The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal anti-factor XII antibody to block contact activation in baboons.  J Clin Invest. 1993;  91 61-68
    CrossrefPubMedSearch in Google Scholar
  • 13 Kalter E S, Daha M R, ten Cate J W, Verhoef J, Bouma B N. Activation and inhibition of Hageman factor-dependent pathways and the complement system in uncomplicated bacteremia or bacterial shock.  J Infect Dis. 1985;  151 1019-1027
    CrossrefPubMedSearch in Google Scholar
  • 14 Ruf W, Edgington T S. Structural biology of tissue factor, the initiator of thrombogenesis in vivo.  FASEB J. 1994;  8 385-390
    PubMedSearch in Google Scholar
  • 15 Mann K G, van't Veer C, Cawthern K, Butenas S. The role of the tissue factor pathway in initiation of coagulation.  Blood Coagul Fibrinolysis. 1998;  9(suppl 1) S3-S7
    PubMedSearch in Google Scholar
  • 16 Camerer E, Kolsto A B, Prydz H. Cell biology of tissue factor, the principal initiator of blood coagulation.  Thromb Res. 1996;  81 1-41
    CrossrefPubMedSearch in Google Scholar
  • 17 Banner D W, D'Arcy A, Chene C et al.. The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor.  Nature. 1996;  380 41-46
    CrossrefPubMedSearch in Google Scholar
  • 18 ten Cate H, Bauer K A, Levi M et al.. The activation of factor X and prothrombin by recombinant factor VIIa in vivo is mediated by tissue factor.  J Clin Invest. 1993;  92 1207-1212
    CrossrefPubMedSearch in Google Scholar
  • 19 Bauer K A, Kass B L, ten Cate H, Hawiger J J, Rosenberg R D. Factor IX is activated in vivo by the tissue factor mechanism.  Blood. 1990;  76 731-736
    PubMedSearch in Google Scholar
  • 20 Østerud B. Tissue factor expression by monocytes: regulation and pathophysiological roles.  Blood Coagul Fibrinolysis. 1998;  9(suppl 1) S9-14
    PubMedSearch in Google Scholar
  • 21 Neumann F J, Marx N, Gawaz M et al.. Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets.  Circulation. 1997;  95 2387-2394
    CrossrefPubMedSearch in Google Scholar
  • 22 Edgington T S, Mackman N, Fan S T, Ruf W. Cellular immune and cytokine pathways resulting in tissue factor expression and relevance to septic shock.  Nouvelle Revue Français d'Hematologie. 1992;  34(suppl) S15-S27
    PubMedSearch in Google Scholar
  • 23 Giesen P L, Rauch U, Bohrmann B et al.. Blood-borne tissue factor: another view of thrombosis.  Proc Natl Acad Sci USA. 1999;  96 2311-2315
    Search in Google Scholar
  • 24 Østerud B, Rao L V, Olsen J O. Induction of tissue factor expression in whole blood-lack of evidence for the presence of tissue factor expression on granulocytes.  Thromb Haemost. 2000;  83 861-867
    PubMedSearch in Google Scholar
  • 25 Nieuwland R, Berckmans R J, McGregor S et al.. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis.  Blood. 2000;  95 930-935
    PubMedSearch in Google Scholar
  • 26 Koyama T, Nishida K, Ohdama S et al.. Determination of plasma tissue factor antigen and its clinical significance.  Br J Haematol. 1994;  87 343-347
    CrossrefPubMedSearch in Google Scholar
  • 27 Taylor F BJ, Chang A, Ruf W et al.. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody.  Circ Shock. 1991;  33 127-134
    PubMedSearch in Google Scholar
  • 28 Biemond B J, Levi M, ten Cate H et al.. Complete inhibition of endotoxin-induced coagulation activation in chimpanzees with a monoclonal Fab fragment against factor VII/VIIa.  Thromb Haemost. 1995;  73 223-230
    PubMedSearch in Google Scholar
  • 29 Zimmerman G A, McIntyre T M, Prescott S M, Stafforini D M. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis.  Crit Care Med. 2002;  30 S294-S301
    CrossrefPubMedSearch in Google Scholar
  • 30 Shebuski R J, Kilgore K S. Role of inflammatory mediators in thrombogenesis.  J Pharmacol Exp Ther. 2002;  300 729-735
    CrossrefPubMedSearch in Google Scholar
  • 31 Broze Jr G J. Tissue factor pathway inhibitor and the revised theory of coagulation.  Annu Rev Med. 1995;  46 103-112
    CrossrefPubMedSearch in Google Scholar
  • 32 Novotny W F, Brown S G, Miletich J P, Rader D J, Broze Jr G J. Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples.  Blood. 1991;  78 387-393
    PubMedSearch in Google Scholar
  • 33 Ameri A, Kuppuswamy M N, Basu S, Bajaj S P. Expression of tissue factor pathway inhibitor by cultured endothelial cells in response to inflammatory mediators.  Blood. 1992;  79 3219-3226
    PubMedSearch in Google Scholar
  • 34 Gando S, Kameue T, Morimoto Y et al.. Tissue factor production not balanced by tissue factor pathway inhibitor in sepsis promotes poor prognosis.  Crit Care Med. 2002;  30 1729-1734
    CrossrefPubMedSearch in Google Scholar
  • 35 Levi M. The imbalance between tissue factor and tissue factor pathway inhibitor in sepsis.  Crit Care Med. 2002;  30 1914-1915
    CrossrefPubMedSearch in Google Scholar
  • 36 Sandset P M, Warn-Cramer B J, Rao L V, Maki S L, Rapaport S I. Depletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation induced with tissue factor: evidence supporting a physiologic role for EPI as a natural anticoagulant.  Proc Natl Acad Sci USA. 1991;  88 708-712
    PubMedSearch in Google Scholar
  • 37 Randolph M M, White G L, Kosanke S D et al.. Attenuation of tissue thrombosis and hemorrhage by ala-TFPI does not account for its protection against E. coli-a comparative study of treated and untreated non-surviving baboons challenged with LD100 E. coli .  Thromb Haemost. 1998;  79 1048-1053
    PubMedSearch in Google Scholar
  • 38 Park C T, Creasey A A, Wright S D. Tissue factor pathway inhibitor blocks cellular effects of endotoxin by binding to endotoxin and interfering with transfer to CD14.  Blood. 1997;  89 4268-4274
    PubMedSearch in Google Scholar
  • 39 de Jonge E, Dekkers P E, Creasey A A et al.. Tissue factor pathway inhibitor (TFPI) dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia.  Blood. 2000;  95 1124-1129
    PubMedSearch in Google Scholar
  • 40 Roque M, Reis E D, Fuster V et al.. Inhibition of tissue factor reduces thrombus formation and intimal hyperplasia after porcine coronary angioplasty.  J Am Coll Cardiol. 2000;  36 2303-2310
    CrossrefPubMedSearch in Google Scholar
  • 41 Creasey A A, Chang A C, Feigen L et al.. Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock.  J Clin Invest. 1993;  91 2850-2856
    CrossrefPubMedSearch in Google Scholar
  • 42 Erlich J H, Boyle E M, Labriola J et al.. Inhibition of the tissue factor-thrombin pathway limits infarct size after myocardial ischemia-reperfusion injury by reducing inflammation.  Am J Pathol. 2000;  157 1849-1862
    CrossrefPubMedSearch in Google Scholar
  • 43 Abraham E, Reinhart K, Svoboda P et al.. Assessment of the safety of recombinant tissue factor pathway inhibitor in patients with severe sepsis: a multicenter, randomized, placebo-controlled, single-blind, dose escalation study.  Crit Care Med. 2001;  29 2081-2089
    CrossrefPubMedSearch in Google Scholar
  • 44 Zoldhelyi P, Chen Z Q, Shelat H S, McNatt J M, Willerson J T. Local gene transfer of tissue factor pathway inhibitor regulates intimal hyperplasia in atherosclerotic arteries.  Proc Natl Acad Sci USA. 2001;  98 4078-4083
    Search in Google Scholar
  • 45 Abraham E, Reinhart K, Opal S et al.. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial.  JAMA. 2003;  290 238-247
    Search in Google Scholar
  • 46 De Pont A C, Moons A H, de Jonge E et al.. Recombinant nematode anticoagulant protein c2, an inhibitor of tissue factor/factor VIIa, attenuates coagulation and the interleukin-10 response in human endotoxemia.  J Thromb Haemost. 2004;  2 65-70
    CrossrefPubMedSearch in Google Scholar
  • 47 Coughlin S R. Thrombin signalling and protease-activated receptors.  Nature. 2000;  407 258-264
    CrossrefPubMedSearch in Google Scholar
  • 48 Cunningham M A, Romas P, Hutchinson P, Holdsworth S R, Tipping P G. Tissue factor and factor VIIa receptor/ligand interactions induce proinflammatory effects in macrophages.  Blood. 1999;  94 3413-3420
    PubMedSearch in Google Scholar
  • 49 Versteeg H H, Peppelenbosch M P, Spek C A. The pleiotropic effects of tissue factor: a possible role for factor VIIa-induced intracellular signalling?.  Thromb Haemost. 2001;  86 1353-1359
    PubMedSearch in Google Scholar
  • 50 de Jonge E, Friederich P W, Levi M, van der Poll T. Activation of coagulation by administration of recombinant factor VIIa elicits interleukin-6 and interleukin-8 release in healthy human subjects.  Clin Diagn Lab Immunol. 2003;  10 495-497
    CrossrefPubMedSearch in Google Scholar
  • 51 Sambrano G R, Weiss E J, Zheng Y W, Huang W, Coughlin S R. Role of thrombin signalling in platelets in haemostasis and thrombosis.  Nature. 2001;  413 74-78
    PubMedSearch in Google Scholar
  • 52 Sabri A, Guo J, Elouardighi H et al.. Mechanisms of protease-activated receptor-4 actions in cardiomyocytes. Role of Src tyrosine kinase.  J Biol Chem. 2003;  278 11714-11720
    CrossrefPubMedSearch in Google Scholar
  • 53 Marutsuka K, Hatakeyama K, Sato Y et al.. Protease-activated receptor 2 (PAR2) mediates vascular smooth muscle cell migration induced by tissue factor/factor VIIa complex.  Thromb Res. 2002;  107 271-276
    CrossrefPubMedSearch in Google Scholar
  • 54 Aird W C. Vascular bed-specific hemostasis: role of endothelium in sepsis pathogenesis.  Crit Care Med. 2001;  29 S28-S34
    CrossrefPubMedSearch in Google Scholar
  • 55 Aird W C, Edelberg J M, Weiler-Guettler H et al.. Vascular bed-specific expression of an endothelial cell gene is programmed by the tissue microenvironment.  J Cell Biol. 1997;  138 1117-1124
    CrossrefPubMedSearch in Google Scholar
  • 56 Rosenberg R D, Aird W C. Vascular-bed-specific hemostasis and hypercoagulable states.  N Engl J Med. 1999;  340 1555-1564
    CrossrefPubMedSearch in Google Scholar
  • 57 Miller D L, Welty-Wolf K, Carraway M S et al.. Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide.  Am J Respir Cell Mol Biol. 2002;  26 650-658
    CrossrefPubMedSearch in Google Scholar
  • 58 Welty-Wolf K E, Carraway M S, Miller D L et al.. Coagulation blockade prevents sepsis-induced respiratory and renal failure in baboons.  Am J Respir Crit Care Med. 2001;  164 1988-1996
    CrossrefPubMedSearch in Google Scholar
  • 59 Moons A H, Levi M, Peters R J. Tissue factor and coronary artery disease.  Cardiovasc Res. 2002;  53 313-325
    CrossrefPubMedSearch in Google Scholar

Marcel LeviM.D. Ph.D. 

Department of Vascular Medicine and Internal Medicine (F-4), Academic Medical Center, University of Amsterdam

Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

Email: m.m.levi@amc.uva.nl