Journal of Molecular Medicine

, Volume 83, Issue 11, pp 876–886

Understanding RAGE, the receptor for advanced glycation end products

  • Angelika Bierhaus
  • Per M. Humpert
  • Michael Morcos
  • Thoralf Wendt
  • Triantafyllos Chavakis
  • Bernd Arnold
  • David M. Stern
  • Peter P. Nawroth
Review

Abstract

Advanced glycation end products (AGEs), S100/calgranulins, HMGB1-proteins, amyloid-β peptides, and the family of β-sheet fibrils have been shown to contribute to a number of chronic diseases such as diabetes, amyloidoses, inflammatory conditions, and tumors by promoting cellular dysfunction via binding to cellular surface receptors. The receptor for AGEs (RAGE) is a multiligand receptor of the immunoglobulin superfamily of cell surface molecules acting as counter-receptor for these diverse molecules. Engagement of RAGE converts a brief pulse of cellular activation to sustained cellular dysfunction and tissue destruction. The involvement of RAGE in pathophysiologic processes has been demonstrated in murine models of chronic disease using either a receptor decoy such as soluble RAGE (sRAGE), RAGE neutralizing antibodies, or a dominant-negative form of the receptor. Studies with RAGE−/− mice confirmed that RAGE contributes, at least in part, to the development of late diabetic complications, such as neuropathy and nephropathy, macrovascular disease, and chronic inflammation. Furthermore, deletion of RAGE provided protection from the lethal effects of septic shock caused by cecal ligation and puncture (CLP). In contrast, deletion of RAGE had no effect on the host response in delayed-type hypersensitivity (DTH). Despite the lack of effect seen in adaptive immunity by the deletion of RAGE, administration of the receptor decoy, sRAGE, still afforded a protective effect in RAGE−/− mice. Thus, sRAGE is likely to sequester ligands, thereby preventing their interaction with other receptors in addition to RAGE. These data suggest that, just as RAGE is a multiligand receptor, its ligands are also likely to recognize several receptors in mediating their biologic effects.

Keywords

RAGE Advanced glycation end products (AGEs) Late diabetic complications Inflammation Innate immunity Pattern recognition receptor 

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Angelika Bierhaus
    • 1
  • Per M. Humpert
    • 1
  • Michael Morcos
    • 1
  • Thoralf Wendt
    • 1
  • Triantafyllos Chavakis
    • 1
  • Bernd Arnold
    • 2
  • David M. Stern
    • 3
  • Peter P. Nawroth
    • 1
  1. 1.Department of Medicine IUniversity of HeidelbergHeidelbergGermany
  2. 2.German Cancer Research InstituteHeidelbergGermany
  3. 3.Medical College of GeorgiaAugustaUSA

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