Retardation of early-onset PMA-induced apoptosis in mouse neutrophils deficient in myeloperoxidase.
Neutrophil apoptosis is a mechanism involved in the resolution of inflammation. To explore the role of hypochlorous acid (HOCl) produced by neutrophils while they are undergoing apoptosis, we compared the rates of apoptosis in neutrophils isolated from normal mice and from myeloperoxidase (MPO)-deficient mice, which are unable to generate HOCl. Apoptosis in MPO-deficient neutrophils stimulated by phorbol myristate acetate (PMA) was significantly slower than in normal neutrophils during 3 h of incubation. Exposure of normal neutrophils to H(2)O(2) together with PMA resulted in a dramatic acceleration of apoptosis, and almost all of the cells revealed apoptotic morphology at 1 h. This acceleration was inhibited by cytochrome c, a superoxide scavenger. Conversely, in MPO-deficient neutrophils activated with PMA and H(2)O(2), little acceleration was observed before 1 h, although it gradually increased thereafter. This retardation was almost completely reversed when MPO or HOCl was exogenously added. These results suggest that coexistence of HOCl and superoxide accelerates the early onset of neutrophil apoptosis.
Tsurubuchi
T
T
Kihara Institute for Biological Research, Yokohama City University, Totsuka, Yokohama 244-0813, Japan.
Aratani
Y
Y
Maeda
N
N
Koyama
H
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D003574:Cytochrome c Group / Q000494:pharmacology; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018375:Neutrophil Activation / Q000502:physiology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D009195:Peroxidase / Q000172:deficiency* / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000975:Antioxidants; D003574:Cytochrome c Group; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate