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

T Tsurubuchi, Y Aratani, N Maeda… - Journal of Leukocyte …, 2001 - academic.oup.com
T Tsurubuchi, Y Aratani, N Maeda, H Koyama
Journal of Leukocyte Biology, 2001academic.oup.com
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 …
Abstract
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.
Oxford University Press