[HTML][HTML] RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides

MA Hofmann, S Drury, C Fu, W Qu, A Taguchi, Y Lu… - Cell, 1999 - cell.com
MA Hofmann, S Drury, C Fu, W Qu, A Taguchi, Y Lu, C Avila, N Kambham, A Bierhaus…
Cell, 1999cell.com
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 (e xtracellular n
ewly 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 …
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 (e xtracellular n ewly 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.
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