Platelets and ATP prime neutrophils for enhanced O2- generation at low concentrations but inhibit O2- generation at high concentrations

Abstract

Platelets are currently thought to play a role in tissue injury and inflammatory states both directly and indirectly through their action on neutrophils (PMNs). Both stimulation and inhibition of PMN superoxide anion (O2-) production by platelets has been reported. To clarify these discrepant observations, we investigated the effects of wide ranges of platelet to PMN ratios as well as concentrations of ATP and ADP on human PMN O2- production. Platelets, at low platelet-to-PMN ratios (1:1 and 5:1), primed PMNs which were stimulated with either FMLP or PMA. However, at higher platelet-to-PMN ratios (25:1, 50:1, and 100:1), inhibition of O2- production was seen. ATP also had a biphasic effect on O2-production: low concentrations of ATP (1 x 10(-6) to 3.2 x 10(-4) M) increased O2-production and high concentrations of ATP (6.4 x 10(-4) M and above) inhibited O2-production. ADP, when added to stimulatory concentrations at ATP, also caused inhibition of O2- production. The incubation time for platelet-neutrophil interactions in vitro was also crucial. Short incubation periods lead to priming, whereas longer periods (greater than 5 min) lead to inhibition. We believe that these studies help to resolve the controversy over the effects of platelets upon the production of O2- by human PMNs and lend further support to the notion that platelets may modulate injury resulting from neutrophil activation.