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(Journal of Leukocyte Biology. 2001;70:52-58.)
© 2001 by Society for Leukocyte Biology

Retardation of early-onset PMA-induced apoptosis in mouse neutrophils deficient in myeloperoxidase

Tetsuto Tsurubuchi^*, Yasuaki Aratani^*, Nobuyo Maeda and Hideki Koyama^*

^* Kihara Institute for Biological Research, Yokohama City University, Totsuka, Yokohama 244-0813, Japan, and
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill

Correspondence: Yasuaki Aratani, Kihara Institute for Biological Research, Yokohama City University, Maioka-cho 641-12, Totsuka, Yokohama 244-0813, Japan. E-mail: yaratani{at}yokohama-cu.ac.jp

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 H₂O₂ 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 H₂O₂, 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.

Key Words: reactive oxygen species • hypochlorous acid • hydrogen peroxide • superoxide • inflammation

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