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Molecular & Cellular Proteomics 5:726-736, 2006.
© 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

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Research

High Expression of Antioxidant Proteins in Dendritic Cells

Possible Implications in Atherosclerosis^*,S

Aymeric Rivollier, Laure Perrin-Cocon, Sylvie Luche, Hélène Diemer^¶, Jean-Marc Strub^¶, Daniel Hanau^||, Alain van Dorsselaer^¶, Vincent Lotteau, Chantal Rabourdin-Combe, Thierry Rabilloud^,** and Christine Servet-Delprat

From the INSERM U503, Université Lyon 1, IFR128-Biosciences Gerland, 21 avenue Tony Garnier, 69 007 Lyon cedex 07, Commissariat à l’Energie Atomique (CEA), Laboratoire d’Immunochimie, DRDC/ICH, INSERM U548, CEA-Grenoble, 17 rue des martyrs, F-38054 Grenoble cedex 9, ^¶ Laboratoire de Spectrométrie de Masse Bio-Organique, UMR CNRS 7509, Ecole de Chimie, Polymères et Matériaux, 25 rue Becquerel, 67008 Strasbourg cedex, and ^|| Biologie des Cellules Dendritiques Humaines, INSERM U725, Etablissement Français du Sang-Alsace, 10 rue Spielmann, 67065 Strasbourg cedex, France

Dendritic cells (DCs) display the unique ability to activate naive T cells and to initiate primary T cell responses revealed in DC-T cell alloreactions. DCs frequently operate under stress conditions. Oxidative stress enhances the production of inflammatory cytokines by DCs. We performed a proteomic analysis to see which major changes occur, at the protein expression level, during DC differentiation and maturation. Comparative two-dimensional gel analysis of the monocyte, immature DC, and mature DC stages was performed. Manganese superoxide dismutase (Mn-SOD) reached 0.7% of the gel-displayed proteins at the mature DC stage. This important amount of Mn-SOD is a primary antioxidant defense system against superoxide radicals, but its product, H₂O₂, is also deleterious for cells. Peroxiredoxin (Prx) enzymes play an important role in eliminating such peroxide. Prx1 expression level continuously increased during DC differentiation and maturation, whereas Prx6 continuously decreased, and Prx2 peaked at the immature DC stage. As a consequence, DCs were more resistant than monocytes to apoptosis induced by high amounts of oxidized low density lipoproteins containing toxic organic peroxides and hydrogen peroxide. Furthermore DC-stimulated T cells produced high levels of receptor activator of nuclear factor B ligand, a chemotactic and survival factor for monocytes and DCs. This study provides insights into the original ability of DCs to express very high levels of antioxidant enzymes such as Mn-SOD and Prx1, to detoxify oxidized low density lipoproteins, and to induce high levels of receptor activator of nuclear factor B ligand by the T cells they activate and further emphasizes the role that DCs might play in atherosclerosis, a pathology recognized as a chronic inflammatory disorder.

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