<Originals>2-Chloroadenosine, a selective inhibitor to mouse macrophages : characteristics of the lethal effect and its mechanism

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In our studies on the effects of purine compounds on immune responses in vitro, we found that 2-chloroadenosine (2-Cl Ado) exhibited a potent lethal effect on a viability of mouse adherent cells derived from peritoneal cavity. The lethal effect was specific for adherent peritoneal cells (macrophages) and prevented by exogenous addition of adenosine (Ado) or coformycin, a potent inhibitor of adenosine deaminase. A rapid decrease of intracellular ATP content (26% of control) in adherent peritoneal cells was observed soon after 1 hr exposure to 2-Cl Ado (0.1mM), and this decrease of ATP was comparable to that of monoiodoacetate (MIA, 0.1mM)-or NaN_3(5mM)-treated adherent peritoneal cells. The ATP decrease by 2-Cl Ado was restored to 88% or 90% of the control value by 1 hr addition of Ado or coformycin, respectively. Polymorphonuclear cells and lymphocytes to which 2-Cl Ado did not exhibit the lethal effect did not cause a significant ATP decrease of the cells. Therefore, the data suggested that the rapid decrease of intracellular ATP content at early time was responsible for the lethal effect of 2-Cl Ado on the adherent PC. We assumed that 2-Cl Ado competed with intracellular Ado in adherent PC and then caused the adenosine starvation resulting in the ATP decrease.
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