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Pentoxifylline inhibition of procoagulant activity generated by activated mononuclear phagocytes
D De Prost1, V Ollivier, J Hakim
1INSERM U 294, CHU Xavier Bichat Paris, France.
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 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.
Insights
Pentoxifylline, a drug, was found to inhibit monocyte blood clotting. This effect appears to be linked to increased cyclic AMP levels within the cells, suggesting a new therapeutic pathway.
Area of Science:
- Immunology
- Hematology
- Pharmacology
Background:
- Monocytes initiate blood coagulation via tissue factor expression.
- This procoagulant activity is implicated in inflammatory responses.
- U937 cells and primary monocytes are relevant models for studying monocyte function.
Purpose of the Study:
- To investigate the effect of pentoxifylline on monocyte procoagulant activity.
- To explore the role of cyclic AMP in pentoxifylline's inhibitory mechanism.
Main Methods:
- Assessing monocyte procoagulant activity in vitro.
- Stimulating monocytes with endotoxin.
- Measuring intracellular cyclic AMP levels.
- Comparing pentoxifylline's effects with other cyclic AMP-elevating compounds.
Main Results:
- Pentoxifylline significantly inhibited endotoxin-induced procoagulant activity in U937 cells and monocytes.
- This inhibition was associated with an early and significant increase in intracellular cyclic AMP levels.
- Compounds known to increase cyclic AMP mimicked the suppressive effect of pentoxifylline.
Conclusions:
- Pentoxifylline suppresses monocyte procoagulant activity.
- The mechanism of action involves, at least in part, an increase in intracellular cyclic AMP.
- This suggests a potential therapeutic role for pentoxifylline in conditions involving monocyte-driven coagulation.