ATP-induced killing of mycobacteria by human macrophages is mediated by purinergic P2Z(P2X7) receptors.
The death of BCG-infected human macrophages induced in vitro by ligation of surface CD95 (Fas), CD69, or complement-mediated lysis was shown not to result in the death of intracellular mycobacteria, whereas exposure to extracellular ATP initiated both macrophage death and killed the intracellular bacteria. ATP acted via P2Z receptors because these effects were mimicked by benzoylbenzoic ATP (a known agonist of P2Z receptors) and blocked by oxidized ATP, DIDS, suramin, amiloride, and KN62 (known inhibitors of P2Z-mediated responses). ATP-mediated bacterial killing was independent of reactive nitrogen and oxygen intermediates and of actinomycin D or cycloheximide inhibition. ATP-induced macrophage cell death, BCG killing, and lucifer yellow dye incorporation were minimal in 2 out of 19 healthy donors. The results suggest possible genetic heterogeneity of this mechanism of mycobacterial killing associated with P2Z-mediated pore formation.
Lammas
D A
DA
Department of Immunology, The Medical School, University of Birmingham, UK.
Stober
C
C
Harvey
C J
CJ
Kendrick
N
N
Panchalingam
S
S
Kumararatne
D S
DS
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000382:microbiology / Q000502:physiology*; D009163:Mycobacterium bovis / Q000276:immunology*; D009584:Nitrogen / Q000378:metabolism / Q000502:physiology; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058486:Receptors, Purinergic P2X7
C546468:P2RX7 protein, human; D017382:Reactive Oxygen Species; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D009584:Nitrogen