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Effects of adenosine on polymorphonuclear leucocyte function, cyclic 3': 5'-adenosine monophosphate, and
1Veterans Administration Medical Center, Boise, Idaho 83702.
Abstract:
1. Inhibition of human polymorphonuclear leucocyte (PMN) function by adenosine was studied with respect to effects of adenosine on intracellular cyclic AMP and calcium during the PMN respiratory burst. 2. The adenosine analogue 5'-N-ethylcarboxamide-adenosine (NECA) and L-N6-phenyl-isopropyl-adenosine (L-PIA) inhibited PMN oxygen metabolite generation with relative potencies (NECA greater than adenosine greater than L-PIA) characteristic of an A2 receptor. 3. The respiratory burst was inhibited by adenosine when PMN were activated by calcium ionophore or chemotactic peptide but not when cells where activated by oleoyl-acetyl-glycerol (OAG). 4. Adenosine increased intracellular cyclic AMP during the PMN respiratory burst regardless of whether cells were stimulated by ionophore, chemotactic peptide or OAG. 5. To determine whether the differences in cell inhibition by adenosine were related to differences in intracellular calcium mobilization by each activating agent, calcium was evaluated with the fluorescent probe, indo-1. Adenosine suppressed the increase in intracellular calcium following PMN activation by calcium ionophore or chemotactic peptide. In contrast, calcium did not increase in PMN activated by OAG and adenosine did not affect intracellular calcium changes following this stimulus. 6. These results demonstrate that physiological concentrations of adenosine inhibit the PMN respiratory burst in association with an increase in intracellular cyclic AMP and reduction of intracellular calcium.
Insights
Adenosine inhibits polymorphonuclear leucocyte (PMN) function by increasing cyclic AMP and reducing intracellular calcium during the respiratory burst. This immune cell modulation is receptor-mediated and stimulus-dependent.
Area of Science:
- Immunology
- Cellular Biology
- Pharmacology
Background:
- Polymorphonuclear leucocytes (PMNs) are crucial immune cells involved in the respiratory burst.
- Adenosine is a nucleoside with known immunomodulatory effects.
- Understanding adenosine's impact on PMN function is vital for inflammatory disease research.
Purpose of the Study:
- To investigate the effects of adenosine on PMN function, specifically intracellular cyclic AMP and calcium levels during the respiratory burst.
- To elucidate the receptor subtypes involved in adenosine-mediated PMN inhibition.
- To determine the relationship between PMN activation stimuli and adenosine's inhibitory effects.
Main Methods:
- Assessed PMN oxygen metabolite generation using adenosine analogues (NECA, L-PIA).
- Measured intracellular cyclic AMP levels in response to various PMN activators (calcium ionophore, chemotactic peptide, OAG).
- Quantified intracellular calcium changes using the fluorescent probe indo-1.
Main Results:
- Adenosine analogues inhibited PMN oxygen metabolite generation, with potencies suggesting A2 receptor involvement.
- Adenosine increased intracellular cyclic AMP irrespective of the activation stimulus.
- Adenosine suppressed intracellular calcium increases when PMNs were activated by calcium ionophore or chemotactic peptide, but not OAG.
Conclusions:
- Physiological adenosine concentrations inhibit the PMN respiratory burst.
- This inhibition is associated with increased intracellular cyclic AMP and reduced intracellular calcium.
- Adenosine's effect on PMN respiratory burst is dependent on the specific activation pathway involved.
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