Superoxide dismutase (SOD) as a potential inhibitory mediator of inflammation via neutrophil apoptosis

Abstract

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.

Phosphorylation of Histone H2AX on Ser 139 and Activation of ATM During Oxidative Burst in Phorbol Ester-Treated Human Leukocytes

“…[39][40][41][42] Experiments were designed, therefore, to test whether the observed H2AX phosphorylation and ATM activation were solely in response to the primary DNA damage induced by oxidative burst and not in response to DNA fragmentation occurring during the course of the cell undergoing apoptosis. Toward this end we have probed caspase activation in PMA-treated cells using FAM-VAD-FMK, the fluorochrome-labeled inhibitor and marker of activation of all caspases.…”

Therapeutic potential of superoxide dismutase (SOD) for resolution of inflammation

“…ROS intermediates and antioxidants are possible regulators of the apoptotic caspases [45,46]. Neutrophils generate reactive oxygen species spontaneously, increasing oxidative stress, which triggers the metabolic cascade and leads to the activation of caspase 3, 8 and 9 in neutrophils, and then induces their apoptosis [18,[45][46][47]. Neutrophil apoptosis is dependent on the production of hydrogen peroxide and caspase-3-dependent mechanisms [18,46,48].…”

“…However, an additional mechanism that may contribute to critical care medicine for the resolution of infl ammation is the regulation of neutrophil apoptosis [17,18]. The clearance of apoptotic neutrophils from sites of infl ammation is a crucial determinant of the resolution of infl ammation [17][18][19]. For the reduction of infl ammation, the activated neutrophils must be removed safely by apoptosis, which suppresses the production of proinfl ammatory cytokines and proteinases, such as neutrophil elastase.…”

The Novel Neutrophil Differentiation Marker Phosphatidylglucoside Mediates Neutrophil Apoptosis

“…The accumulation of ROS may initiate ceramide generation and the clustering of preformed Fas-inducing signaling complexes in lipid rafts (42). SOD enhances spontaneous neutrophil apoptosis, whereas catalase inhibits their spontaneous apoptosis and caspase-3 activation, suggesting that hydrogen peroxide is a potential mediator of ROS-induced neutrophil apoptosis in a caspase-dependent manner (43). Indeed, neutrophils from patients with chronic granulomatous disease, who FIGURE 5.…”