Summary
Inflammatory mediators such as endotoxin can stimulate the expression of procoagulant
activity on both endothelial cells and macrophages while the monokines Interleukin
1, IL-1, and Tumor Necrosis Factor, TNF induce procoagulant activity on endothelial
cells. Incubation of murine peritoneal macrophages with suboptimal concentrations
of endotoxin results in a two fold increase in procoagulant activity. Macrophages
incubated with gamma interferon, IFN γ, or Granulocyte-Macrophage Colony Stimulating
Factor, GM-CSF, for 16 hours prior to endotoxin stimulation demonstrated a synergistic
increase in procoagulant activity. A synergistic increase in procoagulant activity
was also observed with primary cultures of human umbilical cord endothelial cells
incubated with recombinant human IFN γ for 16 hours prior to endotoxin, TNF, or IL-1
stimulation. Human GM-CSF had no stimulatory effect on endotoxin or monokine induced
endothelial cell procoagulant activity. The augmentation of macrophage and endothelial
cell procoagulant activity by IFN γ and GM-CSF may provide a novel explanation for
the role of these cytokines in acute and chronic inflammation.
Keywords
IL-1 - TNF - Endotoxin - Inflammation - Tissue factor