ATP-INDUCED KILLING OF MYCOBACTERIA BY HUMAN MACROPHAGES IS MEDIATED BY PURINERGIC P2Z(P2X(7)) RECEPTORS

The death of BCG-infected human macrophages induced in vitro by ligati on of surface CD95 (Fas), CD69, or complement-mediated lysis was shown not to result in the death of intracellular mycobacteria, whereas exp osure 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 re ceptors) and blocked by oxidized ATP, DIDS, suramin, amiloride, and KN 62 (known inhibitors of P2Z-mediated responses). ATP-mediated bacteria l killing was independent of reactive nitrogen and oxygen intermediate s and of actinomycin D or cycloheximide inhibition. ATP-induced macrop hage cell death, BCG killing, and lucifer yellow dye incorporation wer e minimal in 2 out of 19 healthy donors. The results suggest possible genetic heterogeneity of this mechanism of mycobacterial killing assoc iated with P2Z-mediated pore formation.