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

Wolfgang Speiser; Stylianos Kapiotis; Christoph W. Kopp; Ingrid Simonitsch; Bernd Jilma; Burkhard Jansen; Markus Exner; Andreas Chott

doi:10.1055/s-0037-1615693

Thrombosis and Haemostasis, Table of Contents

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^*

¹Department of Clinical Pharmacology, University of Vienna, Vienna, Austria

³Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Vienna, Austria

,

Stylianos Kapiotis^*

¹Department of Clinical Pharmacology, University of Vienna, Vienna, Austria

³Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Vienna, Austria

,

Christoph W. Kopp

⁴Department of Angiology, University of Vienna, Vienna, Austria

,

Ingrid Simonitsch

²Department of Clinical Pathology, University of Vienna, Vienna, Austria

,

Bernd Jilma

¹Department of Clinical Pharmacology, University of Vienna, Vienna, Austria

,

Burkhard Jansen

¹Department of Clinical Pharmacology, University of Vienna, Vienna, Austria

,

Markus Exner

³Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Vienna, Austria

,

Andreas Chott

²Department of Clinical Pathology, University of Vienna, Vienna, Austria

› Author Affiliations

Abstract

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

Full Text

References

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