Monocytes modulate the fibrinolytic balance of endothelial cells.
Cultured endothelial cells (ECs) produced a constitutive plasminogen activator inhibitor-I (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-1 beta and tumor necrosis factor-alpha. These results indicate that interleukin-1 beta and tumor necrosis factor-alpha induced by the coculture are mostly responsible for decreasing the fibrinolytic activity of ECs.
Funayama
H
H
Department of cardiology, Institute of Hematology, Jichi Medical School, Tochigi, Japan.
Sakata
Y
Y
Kitagawa
S
S
Ikeda
U
U
Takahashi
M
M
Masuyama
J
J
Mimuro
J
J
Matsuda
M
M
Shimada
K
K
D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000378:metabolism*; D005342:Fibrinolysis; D006801:Humans; D007958:Leukocyte Count; D009000:Monocytes / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D017077:Culture Media, Conditioned; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator