Dipyridamole inhibits O2- release and expression of tissue factor activity by peripheral blood monocytes stimulated with lipopolysaccharide.
Monocytes can be induced to synthesize and express tissue factor procoagulant activity. They can also be stimulated to release a broad spectrum of inflammatory agents including superoxide anion (O2-) that are thought to contribute to the pathogenesis of inflammatory diseases. Dipyridamole, an inhibitor of platelet aggregation blocks the lipopolysaccharide (LPS)-induced increase in monocyte-associated tissue factor activity and phorbol myristate acetate (PMA) stimulated O2- release from monocytes and polymorphonuclear leukocytes (PMN). Dipyridamole inhibition of O2- release can be reversed by increased glucose in the culture media, whereas dipyridamole inhibition of tissue factor can not be reversed by increased glucose in the culture media. These results reveal that dipyridamole influences monocytes by at least two distinct mechanisms. Further, it may serve as an anti-thrombotic agent by virtue of its effect on both platelet aggregation and monocyte tissue factor activity.
Brozna
J P
JP
Department of Pathology and Microbiology, University of Nebraska, School of Medicine, Omaha 68198.
Horan
M
M
Carson
S D
SD
D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D004176:Dipyridamole / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013925:Thromboplastin / Q000378:metabolism*
D004731:Endotoxins; D005343:Fibrinolytic Agents; D008070:Lipopolysaccharides; D013481:Superoxides; D004176:Dipyridamole; D013925:Thromboplastin; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate