Activation of the granule pool of the NADPH oxidase accelerates apoptosis in human neutrophils

Oxidative stress induces apoptosis iu many types of cells, including human neutrophils. Our objective was to determine whether reactive oxygen species (ROS) produced by activated neutrophils are associated with accelerated ap optosis, Exposing neutrophils to ionomycin or phorbol myristate acetate (PM A) induced intracellular H2O2 production lid rapid onset of apoptosis, meas ured as condensed chromatin, cellular shrinkage, and DNA fragmentation. Neu trophils activated with formyl-methionyl-leucyl-phenylalanine (fMLP) genera ted mainly extracellular H2O2 and did not undergo apoptosis, Exogenously ad ded H2O2, together with the catalase blocker sodium azide, induced apoptosi s to the same extent and,with similar kinetics as PMA and ionomycin, Adenos ine inhibited ionomycin-induced intracellular H2O2 production and apoptosis . Neither PMA nor ionomycin caused apoptosis in dimethyl sulfoxide-differen tiated HL-60 cells, which are incapable of intracellular H2O2 production, w hereas H2O2 induced apoptosis more efficiently in these cells than in neutr ophils. We propose that activated neutrophils use intracellularly formed H2 O2 to commit suicide.