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 macrophages, we investigated whether ATP(o) has any effect on the viability of chlamydiae in macrophages and, conversely, whether the infection has any effect on susceptibility to ATP(o)-induced killing via P2Z/P2X(7) purinergic receptors. Apoptosis of J774 macrophages could be selectively triggered by ATP(o), because other purine/pyrimidine nucleotides were ineffective, and it was inhibited by oxidized ATP, which irreversibly inhibits P2Z/P2X(7) purinergic receptors. Incubation with ATP(o) but not other extracellular nucleotides inhibits the growth of intracellular chlamydiae, consistent with previous observations on ATP(o) effects on growth of intracellular mycobacteria. However, chlamydial infection for 1 day also inhibits ATP(o)-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 ATP(o) to permeabilize macrophages to small molecules and by abrogating a sustained Ca(2+) influx previously associated with ATP(o)-induced apoptosis.
Coutinho-Silva
R
R
Unité de Biologie des Interactions Cellulaires, Centre National de la Recherche Scientifique, Unité de Recherche Associée 1960, Institut Pasteur, 75724 Paris Cedex 15, France. rcsilva@ibccf.biof.ufrj.br
Perfettini
J L
JL
Persechini
P M
PM
Dautry-Varsat
A
A
Ojcius
D M
DM
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000345:Affinity Labels / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002690:Chlamydia Infections / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002691:Chlamydophila psittaci / Q000187:drug effects / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D009711:Nucleotides / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7
D000345:Affinity Labels; D009711:Nucleotides; C546468:P2RX7 protein, human; C546469:P2rx7 protein, mouse; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D008274:Magnesium