INTERFERON-GAMMA MODULATES THE FIBRINOLYTIC RESPONSE IN CULTURED HUMAN ENDOTHELIAL-CELLS

The fibrinolytic potential of the endothelial cells gives important an tithrombotic properties to the vascular wall. Thrombosis is a frequent complication to atherosclerosis and other conditions where inflammato ry mediators are present in the vascular wall. Inflammatory agents lik e lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF alpha) have been demonstrated to modulate the expression of fibrinolytic fac tors in cultured endothelial cells. In the present study the expressio n of tissue-type plasminogen activator (t-PA), urokinase plasminogen a ctivator (u-PA) and plasminogen activator inhibitors-1 and -2 (PAI-1 a nd PAI-2) antigen in conditioned medium from cultured human umbilical. vein (HUVEC) and human saphenous vein (HSVEC) endothelial cells was i nvestigated under basal conditions and after stimulation with LPS, TNF alpha, interferon-gamma (IFN-gamma) or interleukin-6 (IL-6) alone or in combinations. Stimulation with LPS or TNF alpha increased the expre ssion of PAI-1, u-PA and PAI-2 in HUVEC and HSVEC, while the t-PA resp onse differed between the two cell types. The effects of TNF alpha wer e modulated by IFN-gamma but not by IL-6. The increased expression of u-PA after stimulation with TNF alpha was reduced by IFN-gamma. In con trast, TNF alpha-induced expression of PAI-2 was synergistically incre ased by addition of IFN-gamma. These effects of IFN-gamma represent ad ditional mechanisms by which inflammatory mediators may turn the fibri nolytic potential of the endothelium in a prothrombotic direction.