MONOCYTES MODULATE THE FIBRINOLYTIC BALANCE OF ENDOTHELIAL CELLS

Cultured endothelial cells (ECs) produced a constitutive plasminogen activator inhibitor-1 (PAI-1), whereas primary culture of monocytes from blood did not produce a detectable amount of PAI-1. Addition of monocytes to ECs caused the accumulation of a large amount of PAI-1 in the supernatant in a dose- and time-dependent manner. Having almost no effect on the production of tissue-type plasminogen activator (t-PA), monocytes decreased the potential fibrinolytic activity of ECs. The 6 hours conditioned medium obtained from the coculture system between monocytes and either ECs or paraformaldehyde-fixed ECs had almost the same effect on the other ECs to produce PAI-1 and t-PA as monocytes that were direct contact with ECs. In addition, this effect was specifically inhibited by using two antibodies against interleukin-1β and tumor necrosis factor-α. These results indicate that interleukin-1β and tumor necrosis factor-α induced by the coculture are mostly responsible for decreasing the fibrinolytic activity of ECs. © 1997 Elsevier Science Ltd