Engagement of adenosine receptors inhibits hydrogen peroxide (H 2O 2−) release by activated human neutrophils

Abstract

Adenosine and its analogs, acting at specific cell surface receptors, inhibit generation of superoxide anion by neutrophils. Since it has been suggested that hydrogen peroxide (H 2O 2) release may not be contingent upon superoxide anion release, we studied the effects of 2-chloroadenosine, a potent adenosine receptor agonist, on the formation of H 2O 2 by neutrophils exposed to various stimuli: n-formyl-methionyl-leucyl-phenylalanine (FMLP), concanavalin A, phorbol myristate acetate (PMA), serum-treated zymosan particles (STZ), and immune complexes. 2-Chloroadenosine (0.01 – 10 μ M) inhibited formation of H 2O 2 by neutrophils exposed to FMLP, concanavalin A, and STZ particles. As we have found with O 2 − generation, 2-chloroadenosine failed to inhibit H 2O 2 release by neutrophils stimulated by either phorbol myristate acetate or immune complexes. The data show that whereas adenosine and its analogs inhibit neutrophil release of H 2O 2 and superoxide anion in response to most ligand, they fail to inhibit activation of neutrophils by immune complexes. Nor do they inhibit neutrophil activation by PMA, an agent which bypasses cell surface receptors by direct activation of protein kinase C. Surprisingly, we found that adenosine deaminase activity was adsorbed onto zymosan particles during opsonization and enhanced release of H 2O 2 by neutrophils exposed to STZ. These studies with yeast cell walls suggest that if microorganisms adsorb adenosine deaminase from serum, then the intracellular microbicidal activity of neutrophils is enhanced.