High Expression of Antioxidant Proteins in Dendritic Cells

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 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

An active mitochondrial biogenesis occurs during dendritic cell differentiation

“…Consequently, it can be deduced that during DC differentiation process, taking place in 6-days culture, large increase in the concentration of mitochondrial proteins, such as MnSOD, can occur from marginal increase of the corresponding mRNA levels (Angenieux et al, 2001). Overall, these findings confirmed previous observations (Rivollier et al, 2006) showing that DC are equipped with a very efficient anti-oxidant systems that may assure higher resistance to oxidative environments.…”

Understanding dendritic cell biology and its role in immunological disorders through proteomic profiling

“…In the same study, a high induction of multiple electrophoretic forms of SOD2 during the maturation process of DCs was described, confirming earlier findings by Rivollier et al [65]. The latter study investigated the relation between oxidative stress protein expression profiles and DC differentiation and maturation, making use of 2-DE and MALDI-TOF/TOF-MS. Not only SOD2 was highly expressed in i-and mDCs as compared to monocytes, but also two other important oxidative stress proteins, Prx1 and thioredoxin 1 (Trx1), involved in several cellular redox processes.…”

“…Most of these studies were performed using micro-array analysis and are reviewed elsewhere [54][55][56][57][58][59][60][61][62][63][64][65][66]. With the advent of proteomic approaches, also studies on DCs have been performed at the protein level, resulting in the identification of different proteins that add new information and are complementary to those obtained at the mRNA level.…”

Cutting Edge: Antioxidative Properties of Myeloid Dendritic Cells: Protection of T Cells and NK Cells from Oxygen Radical-Induced Inactivation and Apoptosis

“…In addition, our data reveal that mDCs convey protection against oxidants by increasing thiol expression in lymphocytes by an as yet undefined mechanism. It should be pointed out, however, that recent proteomic-based analyses have revealed that several antioxidative proteins are up-regulated as MPs differentiate into mDCs (34), and multiple mechanisms are therefore likely to contribute to the observed mDC-mediated lymphocyte protection.…”