PMID- 10088602 OWN - NLM STAT- MEDLINE DCOM- 19990325 LR - 20190516 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 65 IP - 2 DP - 1999 Feb TI - Activation of the granule pool of the NADPH oxidase accelerates apoptosis in human neutrophils. PG - 196-204 AB - Oxidative stress induces apoptosis in 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 apoptosis. Exposing neutrophils to ionomycin or phorbol myristate acetate (PMA) induced intracellular H2O2 production and rapid onset of apoptosis, measured as condensed chromatin, cellular shrinkage, and DNA fragmentation. Neutrophils activated with formyl-methionyl-leucyl-phenylalanine (fMLP) generated mainly extracellular H2O2 and did not undergo apoptosis. Exogenously added H2O2, together with the catalase blocker sodium azide, induced apoptosis to the same extent and with similar kinetics as PMA and ionomycin. Adenosine inhibited ionomycin-induced intracellular H2O2 production and apoptosis. Neither PMA nor ionomycin caused apoptosis in dimethyl sulfoxide-differentiated HL-60 cells, which are incapable of intracellular H2O2 production, whereas H2O2 induced apoptosis more efficiently in these cells than in neutrophils. We propose that activated neutrophils use intracellularly formed H2O2 to commit suicide. FAU - Lundqvist-Gustafsson, H AU - Lundqvist-Gustafsson H AD - Division of Pathology II, Faculty of Health Sciences, Linkoping University, Sweden. helen.lundqvist@pod.liu.se FAU - Bengtsson, T AU - Bengtsson T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Ionophores) RN - 53-59-8 (NADP) RN - 56092-81-0 (Ionomycin) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - BBX060AN9V (Hydrogen Peroxide) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Apoptosis/genetics/*physiology MH - DNA Fragmentation MH - Enzyme Activation MH - HL-60 Cells/drug effects/metabolism MH - Humans MH - Hydrogen Peroxide/metabolism/pharmacology MH - Ionomycin/pharmacology MH - Ionophores/pharmacology MH - N-Formylmethionine Leucyl-Phenylalanine/pharmacology MH - NADP/*metabolism MH - Neutrophil Activation MH - Neutrophils/drug effects/enzymology/*physiology MH - Oxidative Stress/physiology MH - Tetradecanoylphorbol Acetate/pharmacology EDAT- 1999/03/24 00:00 MHDA- 1999/03/24 00:01 CRDT- 1999/03/24 00:00 PHST- 1999/03/24 00:00 [pubmed] PHST- 1999/03/24 00:01 [medline] PHST- 1999/03/24 00:00 [entrez] AID - 10.1002/jlb.65.2.196 [doi] PST - ppublish SO - J Leukoc Biol. 1999 Feb;65(2):196-204. doi: 10.1002/jlb.65.2.196.