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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3880-3887. Prepublished online as a Blood First Edition Paper on August 11, 2005; DOI 10.1182/blood-2005-03-1201. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-03-1201v1 106/12/3880    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 Buttari, B. Articles by Riganò, R. Search for Related Content PubMed PubMed Citation Articles by Buttari, B. Articles by Riganò, R. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Phagocytes Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Oxidized 2-glycoprotein I induces human dendritic cell maturation and promotes a T helper type 1 response Brigitta Buttari, Elisabetta Profumo, Vincenzo Mattei, Alessandra Siracusano, Elena Ortona, Paola Margutti, Bruno Salvati, Maurizio Sorice, and Rachele Riganò From the Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome, Italy; and the Dipartimento di Medicina Sperimentale e Patologia, the Laboratorio di Medicina Sperimentale e Patologia Ambientale, Rieti, and the Dipartimento di Scienze Chirurgiche, University "La Sapienza," Rome, Italy. The human plasma protein 2-glycoprotein I (2-GPI) is the most common target for antiphospholipid antibodies associated with thrombotic events in chronic disorders related to endothelial cell dysfunction. Crucial information is needed to clarify why this self-abundant protein is targeted by autoimmune responses. In this study, we investigated whether oxidative modification of 2-GPI, either spontaneous in culture wells or induced by treatment with H2O2, renders this self-protein able to activate immature monocyte-derived dendritic cells (DCs) from healthy human donors. Oxidized 2-GPI caused DCs to mature so that CD83 appeared and CD80, CD86, human leukocyte antigen-D region related (HLA-DR), and CD40 increased. The interaction between oxidized 2-GPI and DCs specifically stimulated these cells to secrete interleukin 12 (IL-12), IL-1, IL-6, IL-8, tumor necrosis factor (TNF-), and IL-10. Oxidized 2-GPI-stimulated DCs had increased allostimulatory ability and primed naive T lymphocytes, thus inducing T helper 1 (Th1) polarization. The interaction between oxidized 2-GPI and DCs involved interleukin-1 receptor associated kinase (IRAK) phosphorylation and nuclear factor B (NFB) activation. Pretreatment of 2-GPI with the antioxidant -tocopherol prevented DC maturation. These findings show that human oxidized 2-GPI, probably by interacting with a member of the Toll-like receptor (TLR) family, causes DCs to mature. Because this key 2-GPI function requires oxidative modification, in several chronic disorders related to endothelial cell dysfunction oxidative stress might trigger the "autoimmune spiral." CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. R. Kroening, T. W. Barnes, L. Pease, A. Limper, H. Kita, and R. 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Siracusano Echinococcus granulosus Antigen B Impairs Human Dendritic Cell Differentiation and Polarizes Immature Dendritic Cell Maturation towards a Th2 Cell Response Infect. Immun., April 1, 2007; 75(4): 1667 - 1678. [Abstract] [Full Text] [PDF] B. Giannakopoulos, F. Passam, S. Rahgozar, and S. A. Krilis Current concepts on the pathogenesis of the antiphospholipid syndrome Blood, January 15, 2007; 109(2): 422 - 430. [Abstract] [Full Text] [PDF] M. K. Mohammad, M. Morran, B. Slotterbeck, D. W. Leaman, Y. Sun, H. v. Grafenstein, S.-C. Hong, and M. F. McInerney Dysregulated Toll-like receptor expression and signaling in bone marrow-derived macrophages at the onset of diabetes in the non-obese diabetic mouse Int. Immunol., July 1, 2006; 18(7): 1101 - 1113. [Abstract] [Full Text] [PDF]

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