Modulation of the chemotactic peptide- and immunoglobulin G-triggered respiratory burst in human neutrophils by exogenous and endogenous adenosine.
The effects of exogenous and endogenous adenosine on the production of oxygen metabolites in neutrophils triggered by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) or immunoglobulin G (IgG)-opsonized yeast particles, were investigated. By using luminol-enhanced chemiluminescence, we found that adenosine A1 receptor activation did not affect, whereas adenosine A receptor activation, through a mechanism involving the cyclic AMP (cAMP)-protein kinase A signalling pathway, both inhibited the fMLP- and IgG-triggered respiratory burst. The adenosine-induced inhibition was however more pronounced after exposure to fMLP than to IgG-yeast. Stimulation with fMLP caused an extracellular accumulation of endogenous adenosine, which indicates that this event is a negative-feedback mechanism preventing an uncontrolled activation of chemoattractant-stimulated neutrophils. On the contrary, exposure of neutrophils to IgG-yeast did not appear to accumulate extracellular adenosine, probably due to increased adenosine deaminase activity during phagocytosis. In conclusion, this work accentuates the importance of adenosine, both exogenously applied and endogenously formed, as an inflammatory agent modulating the respiratory burst during the different phases in neutrophil activation.
Zalavary
S
S
Department of Health and Environment, Faculty of Health Sciences, Linköping University, Sweden. steza@ihm.liu.se
Bengtsson
T
T
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology*; D058892:Adenosine Deaminase Inhibitors; D000248:Adenosine Kinase / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004794:Enzyme Repression; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008165:Luminol / Q000737:chemistry; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015003:Yeasts / Q000737:chemistry
D058892:Adenosine Deaminase Inhibitors; D007074:Immunoglobulin G; D017382:Reactive Oxygen Species; D018047:Receptors, Purinergic P1; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008165:Luminol; D000242:Cyclic AMP; D000248:Adenosine Kinase; D017868:Cyclic AMP-Dependent Protein Kinases; D000241:Adenosine