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.
Highlights
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
This step was our initial main focus as the monocyte-immature dendritic cell transition had been investigated before [40]. These few differences point to well known functions of dendritic cells, such as antigen presentation (HLA class II) or cytokine production (IL1). They point to cytoskeletal remodeling, which is obvious when taking into account the morphological changes between monocytes and immature and mature dendritic cells
One of the most striking differences is Manganese superoxide dismutase (Mn-superoxide dismutase (SOD)). This protein has been described previously as heavily induced during the monocyte-immature DC transition [40], and it is rather surprising to see that despite the high levels reached at this stage, a further induction was observed during DC maturation
Summary
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. Contrary to monocytes and macrophages, the expression pattern of oxidative stress response proteins in DCs is still unknown Both immature and mature DCs have been observed in the atherosclerotic plaques in close association with activated T cells [18] and in para-aortic and jugulodigastric lymph nodes attached to atherosclerotic arterial wall [19], their exact role in atherosclerosis progression is still poorly understood. These studies, suggest that vascular DCs may be implicated in the local induction of immune and autoimmune reactions [20, 21]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
