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Inhibition of macrophage mediated cytotoxicity by exogenous adenosine 5'-triphosphate.

Peripheral blood monocyte derived macrophages from normal donors can be activated with lipopoly-saccharide (LPS) to kill human tumor cells. However, if adenosine 5'-triphosphate (ATP) is added to the macrophage-tumor cell suspensions in micromolar concentrations (10-100 microM), there is marked inhibition of macrophage mediated cytotoxicity. The inhibitory activity was specific to ATP; as it was not demonstrated with GTP, UTP, CTP, AMP or ADP. In addition, this inhibitory activity resulted from an effect of ATP on the effector cells rather than the target cells. When the effector cells were preincubated with ATP they became incapable of killing the tumor cells whereas preincubation of the target cells with ATP had no effect on their ability to be killed by the macrophages. Cytotoxicity was also inhibited when 100 microM of ATP were added to the macrophage monolayers either at the time of addition of the tumor cells or 15-60 min after addition of the tumor cells whereas no inhibition of cytotoxicity occurred when ATP was added more than 1 hr after the initiation of the cytotoxic reaction.