Modulation of P2Z/P2X7receptor activity in macrophages infected withChlamydia psittaci

Abstract

Given the role that extracellular ATP (ATPo)-mediated apoptosis may play in inflammatory responses and in controlling mycobacterial growth in macrophages, we investigated whether ATPohas any effect on the viability of chlamydiae in macrophages and, conversely, whether the infection has any effect on susceptibility to ATPo-induced killing via P2Z/P2X7purinergic receptors. Apoptosis of J774 macrophages could be selectively triggered by ATPo, because other purine/pyrimidine nucleotides were ineffective, and it was inhibited by oxidized ATP, which irreversibly inhibits P2Z/P2X7purinergic receptors. Incubation with ATPobut not other extracellular nucleotides inhibits the growth of intracellular chlamydiae, consistent with previous observations on ATPoeffects on growth of intracellular mycobacteria. However, chlamydial infection for 1 day also inhibits ATPo-mediated apoptosis, which may be a mechanism to partially protect infected cells against the immune response. Infection by Chlamydia appears to protect cells by decreasing the ability of ATPoto permeabilize macrophages to small molecules and by abrogating a sustained Ca2+influx previously associated with ATPo-induced apoptosis.