MODULATION OF THE CHEMOTACTIC PEPTIDE-TRIGGERED 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 peptid e N-formyl-methionyl-leucyl-phenylalanine (fMLP) or immunoglobulin G ( IgG)-opsonized yeast particles, were investigated. By using luminol-en hanced chemiluminescence, we found that adenosine A(1) receptor activa tion did not affect, whereas adenosine A(2) receptor activation, throu gh a mechanism involving the cyclic AMP (cAMP)-protein kinase A signal ling pathway, both inhibited the fMLP- and IgG-triggered respiratory b urst. The adenosine-induced inhibition was however more pronounced aft er exposure to fMLP than to IgG-yeast. Stimulation with fMLP caused an extracellular accumulation of endogenous adenosine, which indicates t hat this event is a negative-feedback mechanism preventing an uncontro lled activation of chemoattractant-stimulated neutrophils. On the cont rary, exposure of neutrophils to IgG-yeast did not appear to accumulat e extracellular adenosine, probably due to increased adenosine deamina se 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 dur ing the different phases in neutrophil activation. (C) 1998 Elsevier S cience B.V. All rights reserved.