Role of mitochondria and reactive oxygen species in dendritic cell differentiation and functions

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【作者】 Annalisa Del Prete  Patrizia Zaccagnino  Marco Di Paola  Maddalena Saltarella  Constanza Oliveros Celis  Beatrice Nico  Giuseppe Santoro  Michele Lorusso 

【关键词】Dendritic cells  Mitochondria  Reactive oxygen species  Oxidative phosphorylation  Free radicals 


【摘要】Dendritic cells (DC) are potent antigen-presenting cells capable of inducing T and B responses and immune tolerance. We have characterized some aspects of energy metabolism accompanying the differentiation process of human monocytes into DC. Compared to precursor monocytes, DC exhibited a much larger number of mitochondria and consistently (i) a higher endogenous respiratory activity and (ii) a more than sixfold increase in ATP content and an even larger increase in the activity of the mitochondrial marker enzyme citrate synthase. The presence in the culture medium of rotenone, an inhibitor of the respiratory chain Complex I, prevented the increase in mitochondrial number and ATP level, without affecting cell viability. Rotenone inhibited DC differentiation, as revealed by the observation that the expression of CD1a, which is a specific surface marker of DC differentiation, was strongly reduced. Cells cultured in the presence of rotenone displayed a lower content of growth factor-induced, mitochondrially generated, hydrogen peroxide. A similar drop in ROS was observed upon addition of catalase, which caused functional effects similar to those produced by rotenone treatment. These results suggest that ROS play a crucial role in DC differentiation and that mitochondria are an important source of ROS in this process.

【刊名】Free Radical Biology and Medicine