Superoxide dismutase (SOD) as a potential inhibitory mediator of inflammation via neutrophil apoptosis.
Superoxide dismutase (SOD) is supposed to be an effective agent for neutrophil-mediated inflammation in the area of critical medicine. We investigated the involvement of SOD in the regulation of neutrophil apoptosis. Exogenously added SOD effectively induced neutrophil apoptosis, and the fluorescence patterns determined using annexin-V and the 7-AAD were similar to those seen in Fas-mediated neutrophil apoptosis. Neutrophils are short-lived leukocytes that need to be removed safely by apoptosis. The clearance of apoptotic neutrophils from sites of inflammation is a crucial determinant of the resolution of inflammation. Catalase inhibited the neutrophil apoptosis and caspase-3 activation. Spontaneous apoptosis, hydrogen peroxide and anti-Fas antibody-induced apoptosis of neutrophils were accelerated in Down's syndrome patients, in whom the SOD gene is overexpressed. Hydrogen peroxide was thought to be a possible major mediator of ROS-induced neutrophil apoptosis in caspase-dependent manner. Neutrophil apoptosis represents a crucial step in the mechanism governing the resolution of inflammation and has been suggested as a possible target for the control of neutrophil-mediated tissue injury. SOD may be a potential inhibitory mediator of neutrophil-mediated inflammation.
Yasui
Kozo
K
Department of Pediatrics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan. k-yasui@hsp.md.shinshu-u.ac.jp
Kobayashi
Norimoto
N
Yamazaki
Takashi
T
Agematsu
Kazunaga
K
Matsuzaki
Satoshi
S
Ito
Susumu
S
Nakata
Setsuko
S
Baba
Atsushi
A
Koike
Kenichi
K
D000328:Adult; D017304:Annexin A5 / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004314:Down Syndrome / Q000097:blood / Q000201:enzymology; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000097:blood; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology*
D017304:Annexin A5; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D017382:Reactive Oxygen Species; C411023:anti-Fas monoclonal antibody; D013482:Superoxide Dismutase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases