%0 Journal Article
%T Auto-protective redox buffering systems in stimulated macrophages
%A Pierre-Jacques Ferret
%A Emmanuelle Soum
%A Olivier Negre
%A Didier Fradelizi
%J BMC Immunology
%D 2002
%I BioMed Central
%R 10.1186/1471-2172-3-3
%X We observed that survivors (10¨C50% depending on the experiments) had acquired a resistant phenotype being capable to survive when further exposed in vitro to an apoptosis inducing dose of the NO donor compound DETA-NO. These cells expressed an increased steady-state levels of Mn SOD, CuZn SOD and catalase mRNA (130¨C200%), together with an increased activity of the corresponding enzymes. Intracellular concentration of glutathione was also increased (¡Á 3.5 fold at 6 hours, still maintained ¡Á 5.2 fold at 48 hours). Neither mRNA for glutathione peroxydase, ¦Ã-glutamylcysteine synthase and glutathione reductase, nor thioredoxine and thioredoxine reductase, were significantly modified. Additional experiments in which RAW 264.7 cells were stimulated with LPS and/or IFN-¦Ã in the presence of relatively specific inhibitors of both Mn and Cu/Zn SOD, aminotriazol (ATZ) catalase inhibitor and buthionine sulfoximine (BSO) glutathione inhibitor, showed that inhibiting LPS-induced up-regulation of intracellular redox buffering systems also prevented acquisition of the resistant phenotype.Our data suggest a direct causal relationship between survival of a fraction of macrophages and a up-regulation of key sets of auto-protective intracellular redox buffering systems, occurring simultaneously with modulation of expression of apoptotic molecules of the Bcl2-Bcl-XL/Bax-Bad family.Macrophages, and their circulating form monocytes, are potent defenders of the integrity of our body by mediating crucial physiological and protective functions. Just to mention some : they are central actors in innate immunity and inflammatory reactions; they process and present foreign antigens either by themselves, or through their lineage descendents; they are also dead cells scavengers. Strikingly, their role as front line defense against myriad of potentially pathogenic infectious agents in the outside environment, is essential in many species from insects to humans. Macrophages use various sets of recept
%U http://www.biomedcentral.com/1471-2172/3/3