Pentoxifylline inhibition of procoagulant activity generated by activated mononuclear phagocytes.
When appropriately stimulated, monocytes are able to initiate blood coagulation through the membrane expression of tissue factor. This procoagulant activity is thought to play a role in activating coagulation in response to inflammatory stimuli in vivo. We found that pentoxifylline, a methylxanthine derivative already reported to regulate some monocyte functions, inhibits the procoagulant activity developed by U937 cells and monocytes in vitro in response to endotoxin. This effect was accompanied by an early increase in intracellular levels of cyclic AMP and was mimicked by compounds that induce an increase in the level of cyclic AMP levels. These results suggest that the suppressive effect of pentoxifylline occurs at least in part via an increase in intracellular cyclic AMP levels.
INSERM U 294, CHU Xavier Bichat Paris, France.
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De Prost
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Ollivier
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Hakim
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001779:Blood Coagulation Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects*; D010431:Pentoxifylline / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001779:Blood Coagulation Factors; D008070:Lipopolysaccharides; C045071:leukocyte procoagulant activity; D003994:Bucladesine; D000242:Cyclic AMP; D010431:Pentoxifylline; D015056:1-Methyl-3-isobutylxanthine