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Mechanisms involved in sodium arsenite‐induced apoptosis of human neutrophils
Author(s) -
William R.,
Watson G.,
Redmond H. Paul,
Wang Jiang Huai,
BouchierHayes David
Publication year - 1996
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 - 10.1002/jlb.60.5.625
Subject(s) - apoptosis , sodium arsenite , catalase , reactive oxygen species , biology , glutathione , arsenite , oxidative stress , propidium iodide , superoxide dismutase , respiratory burst , taurine , biochemistry , microbiology and biotechnology , programmed cell death , chemistry , enzyme , arsenic , organic chemistry , amino acid
Apoptosis is a distinct mechanism by which eukaryotic cells die. Factors governing the induction of polymorphonuclear leukocyte (PMN) apoptosis should be important in understanding resolution of acute inflammation. The mechanisms for induction of PMN apoptosis remain uncertain; however, oxidative stress has been suggested. The aims of this study were to determine whether reactive oxygen intermediates play a role in PMN apoptosis and to investigate inhibition of this process by selective use of antioxidants. PMN were isolated from 10 healthy volunteers. PMN (1 10 6 PMN/mL) were cultured in 40, 80, and 160 μM of arsenite for 2, 6, 12, 18, and 24 h. Apoptosis was assessed qualitatively by morphology and gel electrophoresis and quantitatively by CD16 receptor expression and propidium iodide DNA staining. There was a significant ( P < 0.05) increase in the rate of apoptosis on incubation with arsenite (80 and 160 μM). To investigate the mechanism of this process, intracellular respiratory burst activity was measured following arsenite culture. We found that arsenite‐induced PMN apoptosis correlated with an increase in intracellular respiratory burst. To further investigate the role of oxidative injury in inducing apoptosis, the antioxidants catalase, dimethyl sulfoxide (DMSO), glutathione (GSH), N ‐acetylcysteine (NAC), and taurine were investigated and we demonstrated that GSH, NAC, and taurine were significantly protective against arsenite‐induced apoptosis. However, catalase and DMSO failed to induce protection. This study demonstrates that arsenite induces PMN apoptosis through an oxygen‐dependent mechanism that can be prevented through selective antioxidants. J. Leukoc, Biol . 60: 625–632; 1996.