QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online May 4, 2004
doi: 10.1242/10.1242/jcs.01085

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Elsen, S. Articles by Vignais, P. V. Search for Related Content PubMed PubMed Citation Articles by Elsen, S. Articles by Vignais, P. V.

Cryptic O₂^–-generating NADPH oxidase in dendritic cells

Sylvie Elsen^1,*, Jacques Doussière^1,*, Christian L. Villiers^2,*, Mathias Faure², Rolande Berthier², Anne Papaioannou², Nathalie Grandvaux^1,, Patrice N. Marche^2, and Pierre V. Vignais^1,

¹ Laboratoire de Biochimie et Biophysique des Systèmes Intégrés (UMR 5092 CNRS-CEA-UJF)
² Laboratoire d'Immunochimie (U548 INSERM-CEA-UJF), Département Réponse et Dynamique Cellulaires, CEA-Grenoble, 38054 Grenoble CEDEX 9, France

Authors for correspondence (e-mail: umr5092{at}dsvsud.cea.fr; immuno{at}dsvgre.cea.fr)

Accepted 6 January 2004

All the components of the O₂^–-generating NADPH oxidase typically found in neutrophils, namely a membrane-bound low potential flavocytochrome b and oxidase activation factors of cytosolic origin, are immunodetectable in murine dendritic cells (DCs). However, in contrast to neutrophils, DCs challenged with phorbol myristate acetate (PMA) can barely mount a significant respiratory burst. Nevertheless, DCs generate a substantial amount of O₂^– in the presence of PMA following preincubation with pro-inflammatory ligands such as lipopolysaccharide and pansorbin, and to a lesser extent with anti-CD40 or polyinosinic polycytidylic acid. We found that the virtual lack of the oxidase response to PMA alone is specifically controlled in DCs. Through the use of homologous and heterologous cell-free systems of oxidase activation, we showed the following: (1) a NADPH oxidase inhibitory factor is located in DC membranes; it exerts its effect on oxidase activation and not on the activated oxidase. (2) The inhibition is relieved by pretreatment of DC membranes with ß-octylglucoside (ß-OG). (3) The ß-OG-extracted inhibitory factor prevents the activation of neutrophil oxidase. (4) The inhibitory activity is lost after treatment of DC membranes with proteinase K or heating, which points to the protein nature of the inhibitory factor. Overall, these data indicate that the O₂^–-generating oxidase in DCs is cryptic, owing to the presence of a membrane-bound inhibitor of protein nature that prevents oxidase activation. The inhibition is relieved under specific conditions, including a prolonged contact of DCs with pro-inflammatory ligands from microbial origin, allowing a substantial production of O₂^–, which may contribute to the response of DCs to a microbial exposure.

Key words: Dendritic cell, NADPH oxidase, ROS, Superoxide anion

This article has been cited by other articles:

				F. B. Thoren, A. Betten, A. I. Romero, and K. Hellstrand Cutting Edge: Antioxidative Properties of Myeloid Dendritic Cells: Protection of T Cells and NK Cells from Oxygen Radical-Induced Inactivation and Apoptosis J. Immunol., July 1, 2007; 179(1): 21 - 25. [Abstract] [Full Text] [PDF]

				A. Karlsson, E. Nygren, J. Karlsson, I. Nordstrom, C. Dahlgren, and K. Eriksson Ability of Monocyte-Derived Dendritic Cells To Secrete Oxygen Radicals in Response to Formyl Peptide Receptor Family Agonists Compared to That of Myeloid and Plasmacytoid Dendritic Cells Clin. Vaccine Immunol., March 1, 2007; 14(3): 328 - 330. [Abstract] [Full Text] [PDF]

				K. Bedard and K.-H. Krause The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology Physiol Rev, January 1, 2007; 87(1): 245 - 313. [Abstract] [Full Text] [PDF]

				A. Sinha, A. Singh, V. Satchidanandam, and K. Natarajan Impaired Generation of Reactive Oxygen Species during Differentiation of Dendritic Cells (DCs) by Mycobacterium tuberculosis Secretory Antigen (MTSA) and Subsequent Activation of MTSA-DCs by Mycobacteria Results in Increased Intracellular Survival J. Immunol., July 1, 2006; 177(1): 468 - 478. [Abstract] [Full Text] [PDF]

				A. Rivollier, L. Perrin-Cocon, S. Luche, H. Diemer, J.-M. Strub, D. Hanau, A. van Dorsselaer, V. Lotteau, C. Rabourdin-Combe, T. Rabilloud, et al. High Expression of Antioxidant Proteins in Dendritic Cells: Possible Implications in Atherosclerosis Mol. Cell. Proteomics, April 1, 2006; 5(4): 726 - 736. [Abstract] [Full Text] [PDF]

				E. Billard, C. Cazevieille, J. Dornand, and A. Gross High Susceptibility of Human Dendritic Cells to Invasion by the Intracellular Pathogens Brucella suis, B. abortus, and B. melitensis Infect. Immun., December 1, 2005; 73(12): 8418 - 8424. [Abstract] [Full Text] [PDF]