dangerassociated

Danger-associated is a term used in immunology to refer to danger-associated molecular patterns (DAMPs), endogenous molecules released by stressed, damaged, or dying cells that alert the immune system to tissue injury. DAMPs are recognized by pattern recognition receptors (PRRs) such as Toll-like receptors, NOD-like receptors, and the receptor for advanced glycation end products (RAGE). This recognition triggers signaling cascades that lead to inflammatory cytokine production and recruitment of immune cells. DAMPs differ from pathogen-associated molecular patterns (PAMPs), which originate from microbes.

Common DAMPs include high-mobility group box 1 protein (HMGB1), extracellular ATP, heat shock proteins, uric acid crystals, and mitochondrial DNA. They can be released passively from necrotic cells or actively secreted by stressed cells. DAMP signaling contributes to sterile inflammation, tissue repair, and host defense, but can also promote pathological inflammation in settings such as ischemia-reperfusion injury, autoimmune diseases, and the tumor microenvironment.

Mechanistically, DAMPs activate PRRs, which can trigger NF-κB–mediated transcription and inflammasome activation (e.g., NLRP3), leading to secretion of cytokines like IL-1β and IL-18. Therapeutically, dampening DAMP signaling is an area of interest for reducing harmful inflammation, though complete suppression may impair healing. Interventions under investigation include inhibitors of HMGB1, TLRs, and IL-1 signaling.

The concept arises from the danger model proposed by Polly Matzinger in the 1990s, contrasting the notion that the immune system responds solely to non-self. In current use, DAMPs are a central element in understanding sterile inflammation and inflammatory diseases.