Platelets and ATP Prime Neutrophils for Enhanced 02 Generation at Low Concentrations but Inhibit 02 Generation at High Concentration

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 (02) 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 02 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 02 production was seen. ATP also had a biphasic effect on 02 production: low concentrations of ATP (1 x 106 to 3.2 x i0 M) increased 02 production and high concentrations of ATP (6.4 x iO M and above) inhibited 02 production. ADP, when added to stimulatory concentrations of 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 (> 5 mm) lead to inhibition. We believe that these studies help to resolve the controversy over the effects of platelets upon the production of 02 by human PMNs and lend further support to the notion that platelets may modulate injury resulting from neutrophil activation. Key words: FMLP, PMA, inflammatory response, superoxide productio