Ecto-ATPase: an activation marker necessary for effector cell function

Ecto‐ATPase, a transmembrane enzyme that catalyzes the hydrolysis of extracellular ATP (ATPJ to ADP and inorganic phosphate, is expressed upon cell activation, Ecto‐ATPase is inhibited by non‐hydrolyzable ATP analogues, which are competitive inhibitors of the catalytic reaction, and the ATP analogue affinity label, 5′‐p‐(fluorosulfonyl)benzoyl adenosine (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 ant agonists results in the inhibition of antigen induced cytokine secretion and cytolytic activity of T cells. Likewise, granule release and cytolytic activity of NK cells as well as antibody secretion and spontaneous proliferation by B‐cell hybridomas are inhibited. Inhibition of ecto‐ATPase does not influence effector cell‐target cell conjugate formation, but acts, in part, by regulating the influx of extracellular calcium that is necessary to maintain cellular activation. Thus, further elucidation of ecto‐ATPase regulation and expression and its interaction with intracellular signal transduction events will provide a basis for understanding the role of the hydrolysis of ATPe by ecto‐ATPase in lymphocyte effector function.