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[Inhibition by pentoxifylline of procoagulant activity produced by endotoxin-active monocytes]
D de Prost1, V Ollivier, J Hakim
1Laboratoire d'immunologie et d'hématologie, U INSERM 294, CHU Xavier Bichat, Paris.
Abstract:
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 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 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.
Insights
Pentoxifylline, a drug, inhibits monocyte procoagulant activity by increasing cyclic AMP levels. This finding reveals a novel mechanism for regulating blood coagulation during inflammation.
Area of Science:
- Immunology
- Hematology
- Pharmacology
Context:
- Monocytes play a key role in initiating blood coagulation via tissue factor expression.
- Monocyte procoagulant activity is implicated in inflammatory responses in vivo.
Purpose:
- To investigate the effect of pentoxifylline on monocyte procoagulant activity.
- To elucidate the mechanism underlying pentoxifylline's inhibitory action.
Summary:
- Pentoxifylline, a methylxanthine derivative, was found to inhibit endotoxin-induced procoagulant activity in monocytes in vitro.
- This inhibition correlated with an early rise in intracellular cyclic AMP (cAMP) levels.
- The effect of pentoxifylline was mimicked by other compounds that elevate cAMP.
Impact:
- Suggests that pentoxifylline's suppressive effect on monocyte procoagulant activity is, at least partly, mediated by increased intracellular cAMP.
- Provides potential therapeutic insights for conditions involving monocyte-driven coagulation and inflammation.