Immune cells redox state from mice with endotoxin-induced oxidative stress. Involvement of NF-kappaB.
The immune cells, such as phagocytes and lymphocytes, which use reactive oxygen species (ROS) for carrying out many of their functions, need appropriate levels of intracellular antioxidants to avoid the harmful effect of oxidative stress. In previous studies, we have observed changes in several functions of those leukocytes from female BALB/c mice with lethal endotoxic shock caused by intraperitoneal injection of Escherichia coli 055:B5 lipopolysaccharide (LPS) (100 mg/kg), which were associated with high ROS production. In the present study, we have investigated the redox state of the above mentioned immune cells in that lethal endotoxic shock model measuring the oxidant/antioxidant balance through the following parameters: production of ROS, proinflammatory cytokine TNFalpha reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD) and catalase (CAT) activities, malonaldehyde (MDA) and transcription factor NF-kappaB expression at different times after LPS injection. The results show an increase in ROS, TNFalpha and MDA production in both cell types, being higher in macrophages than in lymphocytes. GSSG/GSH ratio was increased in both macrophages and lymphocytes after LPS injection. With respect to the activity of the antioxidant enzymes SOD and CAT were decreased in both macrophages and lymphocytes. The activation of the transcription factor NF-kappaB was stimulated in macrophages and lymphocytes. These results point out that both lymphocytes and macrophages, which are able to play an important role in host response to endotoxin, show an oxidative stress thus contributing to the pathogenesis of this septic shock.
Victor
Victor M
VM
Department of Animal Physiology, Faculty of Biology, Complutense University, Madrid 28040, Spain. vmvictor@cnic.es
De la Fuente
Monica
M
D000818:Animals; D002374:Catalase / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012772:Shock, Septic / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D019803:Glutathione Disulfide