RAGE Mediates a Novel Proinflammatory Axis: A Central Cell Surface Receptor for S100/calgranulin Polypeptides

Cell. 1999 Jun 25;97(7):889-901. doi: 10.1016/s0092-8674(00)80801-6.

Abstract

S100/calgranulin polypeptides are present at sites of inflammation, likely released by inflammatory cells targeted to such loci by a range of environmental cues. We report here that receptor for AGE (RAGE) is a central cell surface receptor for EN-RAGE (extracellular newly identified RAGE-binding protein) and related members of the S100/calgranulin superfamily. Interaction of EN-RAGEs with cellular RAGE on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Blockade of EN-RAGE/RAGE quenches delayed-type hypersensitivity and inflammatory colitis in murine models by arresting activation of central signaling pathways and expression of inflammatory gene mediators. These data highlight a novel paradigm in inflammation and identify roles for EN-RAGEs and RAGE in chronic cellular activation and tissue injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cattle
  • Colitis / immunology
  • DNA, Complementary
  • Endothelium, Vascular / cytology
  • Female
  • Humans
  • Jurkat Cells
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / immunology
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Peptides / genetics
  • Peptides / immunology*
  • Phagocytes / cytology
  • Phagocytes / immunology
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / immunology*
  • S100 Proteins / genetics
  • S100 Proteins / immunology*
  • S100A12 Protein

Substances

  • DNA, Complementary
  • Membrane Proteins
  • Peptides
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • S100 Proteins
  • S100A12 Protein
  • S100A12 protein, human

Associated data

  • GENBANK/AF011757