title: High expression of antioxidant proteins in dendritic cells: possible implications in atherosclerosis.
abstract: 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, H(2)O(2), 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 kappaB 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 kappaB 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.
authors.affiliation: INSERM U503, Université Lyon 1, IFR128-Biosciences Gerland, 21 avenue Tony Garnier, 69 007 Lyon, France.
authors.forename: Aymeric
authors.initials: A
authors.lastname: Rivollier
authors.forename: Laure
authors.initials: L
authors.lastname: Perrin-Cocon
authors.forename: Sylvie
authors.initials: S
authors.lastname: Luche
authors.forename: Hélène
authors.initials: H
authors.lastname: Diemer
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Strub
authors.forename: Daniel
authors.initials: D
authors.lastname: Hanau
authors.forename: Alain
authors.initials: A
authors.lastname: van Dorsselaer
authors.forename: Vincent
authors.initials: V
authors.lastname: Lotteau
authors.forename: Chantal
authors.initials: C
authors.lastname: Rabourdin-Combe
authors.forename: Thierry
authors.initials: T
authors.lastname: Rabilloud
authors.forename: Christine
authors.initials: C
authors.lastname: Servet-Delprat
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000201:enzymology / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D054464:Peroxiredoxins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D010544:Peroxidases; D054464:Peroxiredoxins; D013482:Superoxide Dismutase