S100A8 and S100A9 inhibit neutrophil oxidative metabolism in-vitro: Involvement of adenosine metabolites

Neutrophils are short-lived granulocytic cells of the innate immune system specialized in the production of reactive oxygen species. S100A8 and S100A9 and their heterocomplex calprotectin play a role in neutrophil recruitment and represent 40% of neutrophil cytosolic protein weight. The present study was designed to test the effect of S100A8 and S100A9 on the rate of neutrophil oxidative metabolism. It is hypothesized that the two S100 proteins inhibit neutrophil associated oxidation. Granulocytes freshly isolated from healthy volunteers were tested for their ability to oxidize dichlorofluorescindiacetate (DCFH-DA) in-vitro. The data showed that S100A8 and S100A9 inhibited spontaneous and stimulated oxidation of the DCFH-DA probe by neutrophils. The inhibition of neutrophil oxidative metabolism by S100A8 and S100A9 was markedly reduced by the enzymatic activity of adenosine deaminase. Inhibitors of the P1 adenosine receptors also reduced the anti-oxidative effect of S100A8/A9 providing further support for the involvement of adenosine metabolites in S100A8/ A9 anti-oxidative effect.