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Thromb Haemost 2001; 85(02): 362-367
DOI: 10.1055/s-0037-1615693
Review Article
Schattauer GmbH

Effect of Intradermal Tumor Necrosis Factor-α-induced Inflammation on Coagulation Factors in Dermal Vessel Endothelium

An In Vivo Study of Human Skin Biopsies
Wolfgang Speiser   *
1   Department of Clinical Pharmacology, University of Vienna, Vienna, Austria
3   Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Vienna, Austria
,
Stylianos Kapiotis   *
1   Department of Clinical Pharmacology, University of Vienna, Vienna, Austria
3   Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Vienna, Austria
,
Christoph W. Kopp
4   Department of Angiology, University of Vienna, Vienna, Austria
,
Ingrid Simonitsch
2   Department of Clinical Pathology, University of Vienna, Vienna, Austria
,
Bernd Jilma
1   Department of Clinical Pharmacology, University of Vienna, Vienna, Austria
,
Burkhard Jansen
1   Department of Clinical Pharmacology, University of Vienna, Vienna, Austria
,
Markus Exner
3   Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Vienna, Austria
,
Andreas Chott
2   Department of Clinical Pathology, University of Vienna, Vienna, Austria
› Author Affiliations
Further Information

Publication History

Received 15 March 2000

Accepted after resubmission 18 August 2000

Publication Date:
08 December 2017 (online)

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Summary

Inflammatory mediators were shown to exert procoagulant effects on cultured human endothelial cells (EC). In the present study the effect of intradermal application of tumor necrosis factor- (TNF-) on the expression of factors involved in regulation of coagulation at the EC surface, i. e. tissue factor (TF), thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI) was studied in humans in vivo. The endothelial expression of these factors was evaluated immunohistochemically in biopsies taken after intradermal application of 5000 U TNF- in 8 healthy volunteers. After 6 and 22 h biopsies were taken from the injection sites. At TNF- injected sites typical inflammatory changes, e. g. EC upregulation of adhesion molecules and accumulation of leukocytes were detected. In parallel we could document EC expression of TF, downregulation of TM and depletion of tissue factor pathway inhibitor (TFPI) in inflamed areas. Early depletion of endothelial I B at the site of inflammation after application of TNF- points to an activation of the NF- B pathway. Our data suggest that, as shown in in vitro experiments, TNF- activates the NF- B pathway and induces specific procoagulant changes of EC due to expression of TF, down-regulation of TM and depletion of TFPI in vivo in humans. This procoagulant shift in the haemostatic balance on the cell surface, caused by TNF- -induced inflammation, is likely to contribute to thrombosis associated with tissue inflammation in humans.

Keywords

TNF-α - human endothelial cell - tissue factor

* These authors contributed equally to this work.


 

  • References

  • 1 Dinarello C. Role of interleukin-1 and tumor necrosis factor in systemic reponse to infection and inflammation. In: Inflammation. Basic principles and clinical correlates. Gallin JI, Goldstein IM, Snyderman R. eds. New York: Raven press; 1992: 211-31.
    Google Scholar
  • 2 Pober JS, Cotran RS. Cytokines and endothelial cell biology. Physiol Rev 1990; 70: 427-51.
    CrossrefPubMedGoogle Scholar
  • 3 Bevilacqua MP, Pober JS, Majeau GR, Fiers W, Cotran RS, Gimbrone Jr MA. Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: Characterization and comparison with the actions of interleukin 1. Proc Natl Acad Sci USA 1986; 83: 4533-7.
    CrossrefPubMedGoogle Scholar
  • 4 Nemerson Y. Tissue factor and haemostasis. Blood 1988; 71: 1-8.
    PubMedGoogle Scholar
  • 5 Moore KL, Esmon CT, Esmon NL. Tumor necrosis factor leads to the internalization and degradation of thrombomodulin from the surface of bovine aortic endothelial cells in culture. Blood 1989; 73: 159-65.
    PubMedGoogle Scholar
  • 6 Esmon CT, Owen WG. Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. Proc Natl Acad Sci USA 1981; 78: 2249-52.
    CrossrefPubMedGoogle Scholar
  • 7 Clouse LH, Comp PC. The regulation of hemostasis: the protein C system. N Engl J Med 1986; 314: 1298-304.
    CrossrefPubMedGoogle Scholar
  • 8 Kirchhofer D, Tschopp TB, Hadvary P, Baumgartner HR. Endothelial cells stimulated with tumor necrosis factor- express varying amounts of tissue factor resulting in inhomogenous fibrin deposition in a native blood flow system. J Clin Invest 1994; 93: 2073-83.
    CrossrefPubMedGoogle Scholar
  • 9 Wun T-C, Kretzmer KK, Girard TJ, Miletich JP, Broze Jr GJ. Cloning and characterization of a cDNA coding for the lipoprotein-associated coagulation inhibitor shows that it consists of three tandem Kunitz inhibitory domains. J Biol Chem 1988; 263: 6001-4.
    PubMedGoogle Scholar
  • 10 Broze GJ, Warren LA, Novotny WF, Higuchi DA, Girard JJ, Miletch JP. The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insights into possible mechanism of action. Blood 1988; 71: 335-43.
    PubMedGoogle Scholar
  • 11 Drake TA, Morrissey JH, Edgington TS. Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am J Pathol 1989; 134: 1087-97.
    PubMedGoogle Scholar
  • 12 Kapiotis S, Jilma B, Szalay T, Eichler HG, Speiser W. Evidence against an effect of endothelin-1 on blood coagulation, fibrinolysis and endothelial cell integrity in healthy men. Arterioscler Thromb Vasc Biol 1997; 17: 2861-7.
    CrossrefPubMedGoogle Scholar
  • 13 More L, Sim R, Hudson M, Dhillon AP, Pounder R, Wakefield AJ. Immunohistochemical study of tissue factor expression in normal intestine and idiopathic inflammatory bowel disease. J Clin Pathol 1993; 46: 703-8.
    CrossrefPubMedGoogle Scholar
  • 14 Lang IM, Mackman N, Kriett JM, Moser KM, Schleef RR. Prothrombotic activation of pulmonary arterial endothelial cells in a patient with tuberculosis. Hum Pathol 1996; 27: 423-7.
    CrossrefPubMedGoogle Scholar
  • 15 Contrino J, Hair G, Kreutzer DL, Rickles FR. In situ detection of tissue factor in vascular endothelial cells: correlation with the malignant phenotype of human breast cancer. Nature Med 1996; 2: 209-15.
    CrossrefPubMedGoogle Scholar
  • 16 Takemura T, Shishiba T, Akiyama O, Oritsu M, Matsui Y, Eishi Y. Vascular involvement in cutaneous sarcoidosis. Pathol Int 1997; 47: 84-9.
    CrossrefPubMedGoogle Scholar
  • 17 Groves RW, Allen MH, Ross EL, Barker JNWN, MacDonald DM. Tumor necrosis factor alpha is pro-inflammatory in normal human skin and modulates cutaneous adhesion molecule expression. Br J Dermatol 1995; 132: 345-52.
    CrossrefPubMedGoogle Scholar
  • 18 Broze Jr GJ, Girard TJ, Novotny WF. Regulation of coagulation by a multivalent Kunitz-type inhibitor. Biochemistry 1990; 29: 7539-46.
    CrossrefPubMedGoogle Scholar
  • 19 Osterud B, Bajaj MS, Bajaj SP. Sites of tissue factor pathway inhibitor (TFPI) and tissue factor expression under physiologic and pathologic conditions. Thromb Haemost 1995; 73: 873-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Ameri A, Kuppuswamy MN, Basu S, Bajaj SP. Expression of tissue factor pathway inhibitor by cultured endothelial cells in response to inflammatory mediators. Blood 1992; 79: 3219-26.
    PubMedGoogle Scholar
  • 21 McGee MP, Foster S, Wang X. Simulatneous expression of tissue factor and tissue factor pathway inhibitor by human monocytes. A potential mechanism for localized control of blood coagulation. J Exp Med 1994; 79: 1847-54.
    PubMedGoogle Scholar
  • 22 Lupu C, Lupu F, Dennehy U, Kakkar VV, Scully MF. Thrombin induces the redistribution and acute release of tissue factor inhibitor from specific granules within human endothelial cells in culture. Arterioscler Thromb Vasc Biol 1995; 15: 2055-62.
    CrossrefPubMedGoogle Scholar
  • 23 Sandset PM, Abildgaard U, Larsen M. Heparin induces release of extrinsic coagulation pathway inhibitor (EPI). Thromb Res 1988; 50: 803-13.
    CrossrefPubMedGoogle Scholar
  • 24 Valentin S, Larnkjer A, Ostergaard P, Nielsen JI, Nordfang O. Characterization of the binding between tissue factor pathway inhibitor and glycosaminoglycans. Thromb Res 1994; 75: 173-83.
    CrossrefPubMedGoogle Scholar
  • 25 Petersen LC, Bjorn SE, Nordfang O. Effect of leukocyte proteinases on tissue factor pathway inhibitor. Thromb Haemost 1992; 67: 537-41.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Mackman N. Regulation of the tissue factor gene. FASEB J 1995; 9: 883-9.
    CrossrefPubMedGoogle Scholar
  • 27 Mackman N. Protease inhibitors block lipopolysaccharide induction of tissue factor gene expression in human monocytic cells by preventing activation of c-Rel/p65 heterodimers. J Biol Chem 1994; 269: 26363-7.
    PubMedGoogle Scholar
  • 28 Henkel T, Machleidt T, Alkalay I, Krönke M, Ben-Nerlah Y, Baeuerle PA. Rapid proteolysis of IκB-αis necessary for activation of transcription factor NF-κB. Nature 1993; 365: 182-5.
    CrossrefPubMedGoogle Scholar
  • 29 Van der Poll T, Büller HR, Ten Cate H, Wortel CH, Bauer KA, Van Deventer SJH, Hack E, Sauerwein HP, Rosenberg RD, Ten Cate JW. Activation of coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med 1990; 322: 1622-7.
    CrossrefPubMedGoogle Scholar
  • 30 Van der Poll T, Levi M, Büller HR, Van Deventer SJH, De Boer JP, Hack E, Ten Cate JW. Fibrinolytic response to tumor necrosis factor in healthy subjects. J Exp Med 1991; 174: 729-32.
    CrossrefPubMedGoogle Scholar