Modulation of P2Z/P2X(7) receptor activity in macrophages infected with Chlamydia psittaci

Given the role that extracellular ATP (ATP(o))-mediated apoptosis may play in inflammatory responses and in controlling mycobacterial growth in macrop hages, we investigated whether ATPo has any effect on the viability of chla mydiae in macrophages and, conversely, whether the infection has any effect on susceptibility to ATP(o)-induced killing via P2Z/P2X(7) purinergic rece ptors. Apoptosis of J774 macrophages could be selectively triggered by ATP( o), because other purine/pyrimidine nucleotides were ineffective, and it wa s inhibited by oxidized ATP, which irreversibly inhibits P2Z/P2X(7) puriner gic receptors. Incubation with ATP(o) but not other extracellular nucleotid es inhibits the growth of intracellular chlamydiae, consistent with previou s observations on ATP(o) effects on growth of intracellular mycobacteria. H owever, chlamydial infection for 1 day also inhibits ATP(o)-mediated apopto sis, which may be a mechanism to partially protect infected cells against t he immune response. Infection by Chlamydia appears to protect cells by decr easing the ability of ATP(o) to permeabilize macrophages to small molecules and by abrogating a sustained Ca2+ influx previously associated with ATP(o )-induced apoptosis.