Related Experiment Videos
Agents that elevate cAMP inhibit human neutrophil apoptosis
A G Rossi1, J M Cousin, I Dransfield
1Department of Medicine, Rayne Laboratory, University of Edinburgh Medical School, UK.
Biochemical and Biophysical Research Communications
|December 26, 1995
Summary
Elevating cyclic AMP (cAMP) levels significantly inhibits neutrophil apoptosis. This finding suggests cAMP plays a key role in controlling neutrophil lifespan and could be a target for therapies.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Neutrophil apoptosis is a critical process for immune homeostasis and resolution of inflammation.
- The role of cyclic AMP (cAMP) in regulating neutrophil apoptosis is not fully understood.
Purpose of the Study:
- To investigate the effect of cAMP-elevating agents on neutrophil apoptosis.
- To explore the involvement of prostaglandin receptors and protein kinase A in this process.
Main Methods:
- Neutrophil apoptosis was assessed using standard criteria and CD16 shedding.
- Cells were treated with cAMP analogs (dibutyryl-cAMP, 8-Br-cAMP), forskolin, and prostaglandin mimetics (ZK 118.182, 11-deoxy PGE1).
- DP-receptor antagonist (BW A868C) and protein kinase A inhibitor (H-89) were used to probe signaling pathways.
Main Results:
- cAMP analogs and forskolin significantly inhibited neutrophil apoptosis in a concentration-dependent manner.
- PGD2 and PGE2 mimetics also demonstrated an inhibitory effect on neutrophil apoptosis.
- The DP-receptor antagonist blocked the effect of ZK 118.182, and H-89 reversed the anti-apoptotic effect of dibutyryl-cAMP.
Conclusions:
- Elevating intracellular cAMP levels markedly attenuates neutrophil apoptosis.
- cAMP signaling pathways, potentially involving prostaglandin receptors and protein kinase A, are crucial regulators of neutrophil longevity.
- Pharmacological modulation of cAMP may offer a strategy to influence neutrophil apoptosis in vivo.