ECTO-ATPASE - AN ACTIVATION MARKER NECESSARY FOR EFFECTOR CELL-FUNCTION

Ecto-ATPase, a transmembrane enzyme chat catalyzes the hydrolysis of e xtracellular ATP (ATP(e)) to ADP and inorganic phosphate, is expressed upon cell activation. Ecto-ATPase is inhibited by non-hydrolyzable AT P analogues, which are competitive inhibitors of the catalytic reactio n, and the ATP analogue affinity label, 5'-p-(fluorosulfonyl)benzoyl a denosine (5'-FSBA), which irreversibly inhibits the catalytic activity . These nucleotide antagonists do not cross the cell membrane and are specific for ecto-ATPase in T cells, B cells and NK cells. Inhibition of ecto-ATPase by both reversible and irreversible nucleotide antagoni sts results in the inhibition of antigen-induced cytokine secretion an d cytolytic activity of T cells. Likewise, granule release and cytolyt ic activity of NK cells as well as antibody secretion and spontaneous proliferation by B-cell hybridomas are inhibited. Inhibition of ecto-A TPase does not influence effector cell-target cell conjugate formation , but acts, in part, by regulating che influx of extracellular calcium that is necessary to maintain cellular activation. Thus, further eluc idation of ecto-ATPase regulation and expression and its interaction w ith intracellular signal transduction events will provide a basis for understanding the role of the hydrolysis of ATP(e) by ecto-ATPase in l ymphocyte effector function.