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Adenosine inhibits superoxide production in rat peritoneal macrophages via elevation of cAMP level
Q S Si1, Y Nakamura, K Kataoka
1Department of Physiology, Ehime University School of Medicine, Japan.
Abstract:
As a part of host-defense immune system, macrophages can response to a variety of stimulants and produce superoxide. We examined the effect of adenosine as a modulator on superoxide production induced by phorbol ester in rat peritoneal macrophages, using an acetyl-cytochrome c reduction method for its detection. 2-Cl-adenosine, a least metabolizable analog of adenosine, inhibited the superoxide production in a dose-dependent manner, and also showed the increasing effect on intracellular cAMP level. Superoxide production was also inhibited by the several reagents which increased intracellular cAMP level, including dibutyryl-cAMP. 8-bromo-cAMP (cell permeable cAMP analogs), forskolin (an adenyl-cyclase activator). Ro 20-1724 (an phosphodiesterase inhibitor), and propentofylline (a xanthine derivative), but not 8-bromo-cGMP (cell permeable cGMP analog). These results suggest that a high level of extracellular adenosine may attenuate immunity through regulating macrophage functions. On the other hand, the tissue damage which is resulted from an over-production of superoxide can be protected by adenosine and its related drugs via an elevation of intracellular cAMP level.
Insights
Adenosine can reduce immune responses by inhibiting superoxide production in macrophages. This effect is linked to increased intracellular cAMP levels, suggesting adenosine may protect against tissue damage from excessive superoxide.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Macrophages are key immune cells involved in host defense.
- Superoxide production by macrophages is a critical component of the immune response.
- Adenosine's role in modulating macrophage function requires further elucidation.
Purpose of the Study:
- To investigate the effect of adenosine on superoxide production in rat peritoneal macrophages.
- To explore the mechanism by which adenosine modulates superoxide production, focusing on intracellular cAMP levels.
Main Methods:
- Rat peritoneal macrophages were stimulated with phorbol ester.
- Superoxide production was quantified using the acetyl-cytochrome c reduction assay.
- The impact of adenosine analogs and cAMP-modulating agents on superoxide production and intracellular cAMP levels was assessed.
Main Results:
- 2-Cl-adenosine, an adenosine analog, inhibited superoxide production in a dose-dependent manner.
- Increased intracellular cAMP levels correlated with reduced superoxide production.
- Agents that elevate cAMP (e.g., dibutyryl-cAMP, forskolin, Ro 20-1724) also inhibited superoxide production, while 8-bromo-cGMP did not.
Conclusions:
- Extracellular adenosine may attenuate immune function by regulating macrophage superoxide production via cAMP signaling.
- Adenosine and related drugs could offer protection against tissue damage caused by excessive superoxide through cAMP elevation.