HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print September 11, 2006

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0306180v1 81/1/59    most recent Alert me when this article is cited Alert me if a correction is posted Services 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 Yang, D. Articles by Oppenheim, J. J. Search for Related Content PubMed PubMed Citation Articles by Yang, D. Articles by Oppenheim, J. J.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0306180

Received for publication March 7, 2006.
Revised May 19, 2006.
Accepted for publication May 22, 2006.

Article

High mobility group box-1 (HMGB1) protein induces the migration and activation of human dendritic cells and acts as an alarmin

De Yang ^*@, Qian Chen ^*, Huan Yang , Kevin J. Tracey , Michael Bustin , and Joost J. Oppenheim ^*

*Laboratory of Molecular Immunoregulation, Center for Cancer Research, and Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Maryland; Laboratory of Biomedical Science, North Shore-Long Island Jewish Research Institute, Manhasset, New York; and Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

^@ To whom correspondence should be addressed. E-mail: dyang{at}ncifcrf.gov.

	Abstract

High mobility group box-1 (HMGB1) protein is a nonhistone, DNA-binding protein that plays a critical role in regulating gene transcription. Recently, HMGB1 has also been shown to act as a late mediator of endotoxic shock and to exert a variety of proinflammatory, extracellular activities. Here, we report that HMGB1 simultaneously acts as a chemoattractant and activator of dendritic cells (DCs). HMGB1 induced the migration of monocyte-derived, immature DCs (Mo-iDCs) but not mature DCs. The chemotactic effect of HMGB1 on iDCs was pertussis toxin-inhibitable and also inhibited by antibody against the receptor of advanced glycation end products (RAGE), suggesting that HMGB1 chemoattraction of iDCs is mediated by RAGE in a Gi protein-dependent manner. In addition, HMGB1 treatment of Mo-iDCs up-regulated DC surface markers (CD80, CD83, CD86, and HLA-A,B,C), enhanced DC production of cytokines (IL-6, CXCL8, IL-12p70, and TNF-), switched DC chemokine responsiveness from CCL5-sensitive to CCL21-sensitive, and acquired the capacity to stimulate allogeneic T cell proliferation. Based on its dual DC-attracting and -activating activities as well as its reported capacity to promote an antigen-specific immune response, we consider HMGB1 to have the properties of an immune alarmin.

Key Words: RAGE • chemotaxis • maturation

This article has been cited by other articles:

				S. Ghavami, I. Rashedi, B. M. Dattilo, M. Eshraghi, W. J. Chazin, M. Hashemi, S. Wesselborg, C. Kerkhoff, and M. Los S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and MAP kinase-dependent pathway J. Leukoc. Biol., June 1, 2008; 83(6): 1484 - 1492. [Abstract] [Full Text] [PDF]

				F. Kappes, J. Fahrer, M. S. Khodadoust, A. Tabbert, C. Strasser, N. Mor-Vaknin, M. Moreno-Villanueva, A. Burkle, D. M. Markovitz, and E. Ferrando-May DEK Is a Poly(ADP-Ribose) Acceptor in Apoptosis and Mediates Resistance to Genotoxic Stress Mol. Cell. Biol., May 15, 2008; 28(10): 3245 - 3257. [Abstract] [Full Text] [PDF]

				A. A. Manfredi, A. Capobianco, A. Esposito, F. De Cobelli, T. Canu, A. Monno, A. Raucci, F. Sanvito, C. Doglioni, P. P. Nawroth, et al. Maturing Dendritic Cells Depend on RAGE for In Vivo Homing to Lymph Nodes J. Immunol., February 15, 2008; 180(4): 2270 - 2275. [Abstract] [Full Text] [PDF]

				C. K. Zetterstrom, W. Jiang, H. Wahamaa, T. Ostberg, A.-C. Aveberger, H. Schierbeck, M. T. Lotze, U. Andersson, D. S. Pisetsky, and H. Erlandsson Harris Pivotal Advance: Inhibition of HMGB1 nuclear translocation as a mechanism for the anti-rheumatic effects of gold sodium thiomalate J. Leukoc. Biol., January 1, 2008; 83(1): 31 - 38. [Abstract] [Full Text] [PDF]

				B. Moser, D. D. Desai, M. P. Downie, Y. Chen, S. F. Yan, K. Herold, A. M. Schmidt, and R. Clynes Receptor for Advanced Glycation End Products Expression on T Cells Contributes to Antigen-Specific Cellular Expansion In Vivo J. Immunol., December 15, 2007; 179(12): 8051 - 8058. [Abstract] [Full Text] [PDF]

				A. Tsung, J. R. Klune, X. Zhang, G. Jeyabalan, Z. Cao, X. Peng, D. B. Stolz, D. A. Geller, M. R. Rosengart, and T. R. Billiar HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling J. Exp. Med., November 26, 2007; 204(12): 2913 - 2923. [Abstract] [Full Text] [PDF]

				J. V. Raelson, R. D. Little, A. Ruether, H. Fournier, B. Paquin, P. Van Eerdewegh, W. E. C. Bradley, P. Croteau, Q. Nguyen-Huu, J. Segal, et al. From the Cover: Genome-wide association study for Crohn's disease in the Quebec Founder Population identifies multiple validated disease loci PNAS, September 11, 2007; 104(37): 14747 - 14752. [Abstract] [Full Text] [PDF]