ABSTRACT

This chapter describes the changes in anticoagulant properties of endothelial cells after exposure to Tumor necrosis factor (TNF-a) and subsequently focuses on the alterations in the fibrinolytic system induced by TNF-a in vitro and in vivo. TNF-a was originally proposed as a factor responsible for the hemorrhagic necrosis of tumors, which was occasionally observed after injection of bacteria or bacterial cell wall products in tumor-bearing animals. The fibrinolytic activity in blood is largely determined by the concentration of tissue-type plasminogen activator, and is modulated by, among others, plasminogen activator inhibitor type 1. Endothelial cells adapt their properties and responses after being challenged by cytokines or other biological response modifiers. The antithrombotic properties of endothelial cells in vitro are affected by TNF-a. In cultured endothelial cells TNF-a induces the expression of tissue factor and reduces thrombomodulin activity on the surface of the cell.