MONOCYTES MODULATE THE FIBRINOLYTIC BALANCE OF ENDOTHELIAL-CELLS

Cultured endothelial cells (ECs) produced a constitutive plasminogen a ctivator inhibitor-1 (PAI-1), whereas primary culture of monocytes fro m blood did not produce a detectable amount of PAI-1. Addition of mono cytes to: ECs caused the accumulation of a large amount of PAI-1 in th e supernatant in a dose- and time-dependent manner. Having almost no e ffect on the production of tissue-type plasminogen activator (t-PA), m onocytes decreased the potential fibrinolytic activity of ECs. The 6 h ours conditioned medium obtained from the coculture system between mon ocytes and either ECs or paraformaldehyde-fixed ECs had almost the sam e 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 specificall y inhibited by using two antibodies against interleukin-1 beta and tum or necrosis factor-alpha. These results indicate that interleukin-1 be ta and tumor necrosis factor-alpha induced by the coculture are mostly responsible for decreasing the fibrinolytic activity of ECs. (C) 1997 Elsevier Science Ltd.