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Prevention of tissue factor generation in mononuclear cells by agents known to increase intracellular cyclic AMP
Abstract:
Agents known to increase intracellular levels of cyclic 3', 5'-adenosine monophosphate (cyclic AMP) were examined for their effect on tissue factor generation by mononuclear cells cultured with E. coli endotoxin. Aminophylline, an inhibitor of phosphodiesterase, and epinephrine, a beta-adrenergic agent, showed an inhibitory effect, and these effects were reversible. Moreover, dibutyryl cyclic AMP also exhibited the effect. Dibutyryl cyclic GMP, however, did not enhance the tissue factor generation by mononuclear cells. On the basis of these observations, it was concluded that the phenomenon of tissue factor generation by mononuclear cells is a biological event, and that intracellular cyclic AMP has a possible role in modulating this phenomenon.
Insights
Agents that boost cyclic adenosine monophosphate (cyclic AMP) levels inhibited tissue factor generation by mononuclear cells. This suggests cyclic AMP plays a role in modulating this crucial biological event.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Tissue factor generation by mononuclear cells is a critical process in hemostasis and inflammation.
- The role of intracellular signaling molecules in regulating this process is not fully understood.
Purpose of the Study:
- To investigate the effect of agents increasing intracellular cyclic adenosine monophosphate (cyclic AMP) levels on tissue factor generation by mononuclear cells stimulated with E. coli endotoxin.
Main Methods:
- Mononuclear cells were cultured with E. coli endotoxin.
- Agents known to increase cyclic AMP, including aminophylline, epinephrine, and dibutyryl cyclic AMP, were added.
- The effect on tissue factor generation was assessed.
- Dibutyryl cyclic GMP was used as a control.
Main Results:
- Aminophylline (a phosphodiesterase inhibitor) and epinephrine (a beta-adrenergic agent) significantly inhibited tissue factor generation.
- These inhibitory effects were reversible.
- Dibutyryl cyclic AMP also demonstrated an inhibitory effect.
- Dibutyryl cyclic GMP did not enhance tissue factor generation.
Conclusions:
- Intracellular cyclic AMP levels appear to modulate the generation of tissue factor by mononuclear cells.
- This finding highlights a potential regulatory mechanism in the biological event of tissue factor production.