High expression of antioxidant proteins in dendritic cells: possible implications in atherosclerosis.
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.
Rivollier
Aymeric
A
INSERM U503, Université Lyon 1, IFR128-Biosciences Gerland, 21 avenue Tony Garnier, 69 007 Lyon, France.
Perrin-Cocon
Laure
L
Luche
Sylvie
S
Diemer
Hélène
H
Strub
Jean-Marc
JM
Hanau
Daniel
D
van Dorsselaer
Alain
A
Lotteau
Vincent
V
Rabourdin-Combe
Chantal
C
Rabilloud
Thierry
T
Servet-Delprat
Christine
C
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
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