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

  1. Author:
    Yang, D.
    Chen, Q.
    Yang, H.
    Tracey, K. J.
    Bustin, M.
    Oppenheim, J. J.

  2. Author Address

    SAIC Frederick Inc, Basic Res Program, NCI, Frederick, MD 21702 USA. Ctr Canc Res, Mol Immunoregulat Lab, Frederick, MD USA. N Shore Long Isl Jewish Res Inst, Lab Biomed Sci, Manhasset, NY USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.;Yang, D, SAIC Frederick Inc, Basic Res Program, NCI, Rm 31-19,Bldg 560,1050 Boyles St, Frederick, MD 21702 USA.;dyang@ncifcrf.gov
    1. Year: 2007
    2. Date: Jan
  2. Journal: Journal of Leukocyte Biology
    1. 81
    2. 1
    3. Pages: 59-66
  4. Type of Article: Article
  5. ISSN: 0741-5400
  1. Abstract:

    High mobility group hox-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 alpha), 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.

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External Sources

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  2. DOI: 10.1189/jlb.0306180
  3. View record in Web of Science®
  4. WOS: 000243187800009

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