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Adenosine and 2-phenylaminoadenosine (CV-1808) inhibit human neutrophil bactericidal function
G E Hardart1, G W Sullivan, H T Carper
1Department of Medicine, University of Virginia, Charlottesville 22908.
Infection and Immunity
|March 1, 1991
Summary
Adenosine and its analog CV-1808 impair polymorphonuclear neutrophil (PMN) killing of Staphylococcus aureus by reducing superoxide release. Physiological adenosine levels do not affect PMN function, but pharmacological doses may increase infection susceptibility.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Adenosine acts as an endogenous immunomodulator with anti-inflammatory properties.
- Polymorphonuclear neutrophils (PMNs) are crucial for host defense against bacterial infections.
- Soluble stimuli can inhibit the PMN oxidative burst, a key component of their bactericidal function.
Purpose of the Study:
- To investigate the impact of adenosine and its analog CV-1808 on the bactericidal capacity of PMNs.
- To determine if these compounds affect PMN interaction with Staphylococcus aureus or their ability to kill bacteria.
Main Methods:
- Human PMNs were incubated with Staphylococcus aureus in the presence of adenosine or CV-1808.
- Bacterial killing was assessed by quantifying surviving bacteria after incubation.
- Superoxide release from activated PMNs was measured.
- The effect of inosine, a major adenosine metabolite, was also evaluated.
Main Results:
- Adenosine (10 mM) and CV-1808 (10-100 µM) significantly inhibited PMN killing of S. aureus.
- Bacterial killing was reduced by 254% with adenosine and 739% with CV-1808 compared to controls.
- Adenosine and CV-1808 decreased S. aureus-activated PMN superoxide release.
- Inosine did not affect bacterial killing.
- These effects were observed at concentrations significantly higher than physiological levels of adenosine.
Conclusions:
- Pharmacological concentrations of adenosine and its analogs can impair PMN bactericidal function by inhibiting superoxide release.
- While endogenous adenosine is unlikely to compromise PMN defense, elevated levels from therapeutic agents could potentially increase susceptibility to infections.