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ATP-induced killing of mycobacteria by human macrophages is mediated by purinergic P2Z(P2X7) receptors

D A Lammas1, C Stober, C J Harvey

  • 1Department of Immunology, The Medical School, University of Birmingham, UK.

Immunity
|November 5, 1997
PubMed

Insights

Extracellular ATP triggers human macrophage death and kills intracellular BCG bacteria via P2Z receptors. This mechanism, potentially linked to genetic variations, offers a new avenue for mycobacterial infection research.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Macrophage death pathways are crucial for controlling intracellular pathogens like Mycobacterium bovis bacillus Calmette-Guérin (BCG).
  • Previous studies indicated that surface receptor ligation or complement lysis of macrophages does not eliminate intracellular mycobacteria.

Purpose of the Study:

  • To investigate the effect of extracellular adenosine triphosphate (ATP) on intracellular BCG survival within human macrophages.
  • To elucidate the mechanism of ATP-mediated macrophage death and bacterial killing.

Main Methods:

  • Human macrophages infected with BCG were treated with extracellular ATP or other stimuli (CD95, CD69, complement).
  • ATP's mechanism was explored using P2Z receptor agonists (benzoylbenzoic ATP) and inhibitors (oxidized ATP, DIDS, suramin, amiloride, KN62).
  • Bacterial killing was assessed independently of reactive oxygen/nitrogen species and protein synthesis inhibitors.

Main Results:

  • Extracellular ATP induced both macrophage death and killing of intracellular BCG.
  • ATP's effects were mediated through P2Z receptors, as confirmed by agonist and inhibitor studies.
  • ATP-induced cell death and BCG killing showed minimal activity in a subset of healthy donors, suggesting genetic heterogeneity.

Conclusions:

  • Extracellular ATP is a potent inducer of P2Z receptor-mediated macrophage death and intracellular BCG killing.
  • The observed variability in response among donors points to a potential genetic basis for P2Z receptor function in mycobacterial killing.
  • This finding opens new perspectives for understanding host-pathogen interactions and developing novel therapeutic strategies against mycobacterial infections.

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