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Retardation of early‐onset PMA‐induced apoptosis in mouse neutrophils deficient in myeloperoxidase
Author(s) -
Tsurubuchi Tetsuto,
Aratani Yasuaki,
Maeda Nobuyo,
Koyama Hideki
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.70.1.52
Subject(s) - myeloperoxidase , apoptosis , cytochrome c , hypochlorous acid , superoxide , phorbol , biology , granulocyte , neutrophile , inflammation , reactive oxygen species , microbiology and biotechnology , immunology , biochemistry , enzyme , protein kinase c
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.