The cellular distribution of extracellular superoxide dismutase in macrophages is altered by cellular activation but unaffected by the naturally occurring R213G substitution

Abstract

Extracellular superoxide dismutase (EC-SOD) is responsible for the dismutation of the superoxide radical produced in the extracellular space and known to be expressed by inflammatory cells, including macrophages and neutrophils. Here we show that EC-SOD is produced by resting macrophages and associated with the cell surface via the extracellular matrix (ECM)-binding region. Upon cellular activation induced by lipopolysaccharide, EC-SOD is relocated and detected both in the cell culture medium and in lipid raft structures. Although the secreted material presented a significantly reduced ligand-binding capacity, this could not be correlated to proteolytic removal of the ECM-binding region, because the integrity of the material recovered from the medium was comparable to that of the cell surface-associated protein. The naturally occurring R213G amino acid substitution located in the ECM-binding region of EC-SOD is known to affect the binding characteristics of the protein. However, the analysis of macrophages expressing R213G EC-SOD did not present evidence of an altered cellular distribution. Our results suggest that EC-SOD plays a dynamic role in the inflammatory response mounted by activated macrophages.

N‐Glycosylation is essential for the secretion of extracellular superoxide dismutase

“…Although the cell anchorage and release from the matrix of EC-SOD have received much attention, the regulatory mechanisms of intracellular trafficking of EC-SOD have remained poorly understood. In contrast, upon activation by lipopolysaccharide, EC-SOD seemed to be relocated to the lipid rafts and secreted by an unknown mechanism [43]. In resting primary mouse macrophages, EC-SOD is not A B Fig.…”

The R213G polymorphism in SOD3 protects against allergic airway inflammation

“…(42)(43)(44)(45)(46)(47). Allergic asthma, oxidative stress, and lung inflammation go hand-in-hand (48,49).…”

Plant Extracts and Plant-Derived Compounds: Promising Players in Countermeasure Strategy Against Radiological Exposure: A Review

“…Table 1 shows that many of them act by scavenging ROS and other free radicals, and by decreasing the radiation-induced increase in the level of TGF-β1, TNF-α, IFN-γ, WBC influx in tissue, IL-1β, IL-2, IL-4, IL-6, IL-12, IL-17, MIP-1α, VEGF, etc, all of them being key players in inflammatory response (Xie et al, 2006;Kim et al, 2007;Lee et al, 2007;Day et al, 2008;Qiu et al, 2008;Christofidou-Solomidou et al, 2011;Hei et al, 2011;Janko et al, 2012;Monceau et al, 2013;Pragya et al, 2014). Others act against radiation exposure by inducing the expression of Mn-SOD, GSH, CAT, and GPx, the important members of antioxidant defence system (Han et al, 2005;Gottfredsen et al, 2014) or modulate the immune response against radiation exposure Qiu et al, 2008;Pragya et al, 2014;Yu et al, 2014). Additionally, some of these plant extract/plant-derived compounds have also been found to reduce ROS, suppress cytokines, TNF-α and TGF-β1, thereby reducing the OH-proline level (the fibrotic index) in radiation-induced lung tissue (Han et al, 2006;Xie et al, 2006;Lee et al, 2009;Lee et al, 2010;Flechsig et al, 2010;Qiu et al, 2011;Gorshkova et al, 2012;Cho et al, 2013;Ding et al, 2013;Horton et al, 2013).…”

“…GPx activity was also increased (p<0.001) by administration of ginsan before irradiation, compared with irradiated controls, again corroborating the results of mRNA and protein expression. Since certain types of SOD are known to be modulated by components of immune system (Qiu et al, 2008;Gottfredsen et al, 2014;Pragya et al, 2014;Yu et al, 2014), it is possible that activation of the antioxidant enzymes by ginsan as seen above, could have been alteration in cytokines, TGF-β, etc., thereby conferring radiological protection. This proposition appears to be supported by work of Kim et al (2007).…”