Induction of endothelial cell/macrophage procoagulant activity: synergistic stimulation by gamma interferon and granulocyte-macrophage colony stimulating factor.
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 gamma, 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 gamma 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 gamma and GM-CSF may provide a novel explanation for the role of these cytokines in acute and chronic inflammation.
Zuckerman
S H
SH
Department of Immunology, Lilly Research Labs, Indianapolis, IN 46285.
Suprenant
Y M
YM
D000818:Animals; D001779:Blood Coagulation Factors / Q000096:biosynthesis*; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D013925:Thromboplastin
D001779:Blood Coagulation Factors; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D008070:Lipopolysaccharides; C053675:endothelial cell procoagulant activity; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013925:Thromboplastin