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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4712-4722. Prepublished online as a Blood First Edition Paper on August 5, 2008; DOI 10.1182/blood-2008-01-134791. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-01-134791v1 112/12/4712    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mantegazza, A. R. Articles by Amigorena, S. Search for Related Content PubMed PubMed Citation Articles by Mantegazza, A. R. Articles by Amigorena, S. Related Collections Phagocytes Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES NADPH oxidase controls phagosomal pH and antigen cross-presentation in human dendritic cells Adriana R. Mantegazza1, Ariel Savina1, Mónica Vermeulen2, Laura Pérez3, Jorge Geffner2, Olivier Hermine4, Sergio D. Rosenzweig3, Florence Faure1, and Sebastián Amigorena1 1 Inserm U653 Immunité et cancer, Institut Curie, Paris, France; 2 Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina; 3 Servicio de Immunología, Hospital Garrahan, Buenos Aires, Argentina; and 4 Centre National de Recherche Scientifique (CNRS) UMR 8147, Hôpital Necker-Enfants-Malades, Paris, France The phagocyte NADPH oxidase (NOX2) is critical for the bactericidal activity of phagocytic cells and plays a major role in innate immunity. We showed recently that NOX2 activity in mouse dendritic cells (DCs) prevents acidification of phagosomes, promoting antigen cross-presentation. Inorder to investigate the role of NOX2 in the regulation of the phagosomal pH in human DCs, we analyzed the production of reactive oxygen species (ROS) and the phagosomal/endosomal pH in monocyte-derived DCs and macrophages (MØs) from healthy donors or patients with chronic granulomatous disease (CGD). As expected, we found that human MØs acidify their phagosomes more efficiently than human DCs. Accordingly, the expression of the vacuolar proton ATPase (V-H+-ATPase) was higher in MØs than in DCs. Phagosomal ROS production, however, was also higher in MØs than in DCs, due to higher levels of gp91phox expression and recruitment to phagosomes. In contrast, in the absence of active NOX2, the phagosomal and endosomal pH decreased. Both in the presence of a NOX2 inhibitor and in DCs derived from patients with CGD, the cross-presentation of 2 model tumor antigens was impaired. We conclude that NOX2 activity participates in the regulation of the phagosomal and endosomal pH in human DCs, and is required for efficient antigen cross-presentation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Crosspresentation: a matter of pH Alessio Nencioni and Peter Brossart Blood 2008 112: 4368-4369. [Full Text] [PDF] This article has been cited by other articles: O. H. Vandal, C. F. Nathan, and S. Ehrt Acid Resistance in Mycobacterium tuberculosis J. Bacteriol., August 1, 2009; 191(15): 4714 - 4721. [Full Text] [PDF] J. Huang, V. Canadien, G. Y. Lam, B. E. Steinberg, M. C. Dinauer, M. A. O. Magalhaes, M. Glogauer, S. Grinstein, and J. H. Brumell Activation of antibacterial autophagy by NADPH oxidases PNAS, April 14, 2009; 106(15): 6226 - 6231. [Abstract] [Full Text] [PDF]

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