Role of oxygen radicals in tissue factor induction by endotoxin in blood monocytes.
In response to bacterial endotoxin (lipopolysaccharide, LPS) monocytes synthesize and express on their surface tissue factor (TF) which triggers the blood coagulation cascade. Since LPS stimulates active oxygen species production by these cells, we investigated the roles of superoxide anion and nitric oxide in the induction of TF in human blood monocytes. Scavengers of reactive oxygen intermediates such as N-acetyl cysteine or pyrrolidine dithiocarbamate were able to block TF induction. In addition, inhibition of NADPH oxidase and/or NO synthase which are major sources of active oxygen species in phagocytes also blocked TF induction. The restoration of TF expression, in monocytes treated with inhibitors of reactive oxygen production, by N,N'-dimethyl-gamma, gamma'-dipyridylium dichloride and/or sodium nitrosylpentacyanoferrate (III), which generate respectively O2- and NO, suggests that these two radicals participate in the induction of TF at the surface of blood monocytes stimulated by LPS.
Polack
B
B
Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Grenoble, France. Benoit.Polack@ujf-grenoble.fr
Pernod
G
G
Barro
C
C
Doussière
J
J
D004357:Drug Synergism; D004731:Endotoxins / Q000097:blood / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009569:Nitric Oxide / Q000138:chemical synthesis / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000502:physiology*; D013481:Superoxides / Q000494:pharmacology; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D004731:Endotoxins; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D013481:Superoxides; D009569:Nitric Oxide; D013925:Thromboplastin; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases