Schematic depiction of a role for RAGE and its ligands (especially S100/calgranulins) at the site of a chronic immune/inflammatory response. We hypothesize that S100/calgranulin-RAGE interaction provides a mechanism amplifying the inflammatory response by mediating activation of RAGE-bearing cells, including mononuclear phagocytes, lymphocytes, and cells in the vessel wall. In contrast, RAGE and its ligands are not the trigger for initiating the host response, which may be due to primary immune, inflammatory, or infectious stimuli.