Damp

Acronym for "danger-associated molecular pattern". The term DAMP or DAMPs or alarmins refers to non-microbial pathogens that lead to the release of inflammatory mediators such as interleukin-1beta and interleukin-18 in the organism. Pathogen-associated molecular patterns, or PAMPs for short, are distinguished from DAMPs.

These can be different pathogens such as extracellular ATP (from destroyed or activated cells), heat shock proteins, cold shock proteins, antimicrobial peptides, S100 proteins, but also crystalline structures such as asbestos, silicon oxide, uric acid, calcium pyrophosphate or cholesterol crystals) or reactive oxygen species (ROS).

Further examples are: HMGB1 (High-Mobility Group Protein 1), HDGF (hepatoma-derived growth factor), interleukin-1, cathelicidins, defensins, galectins, thymosins, TSLP (thymic stromal lymphopoietin - see also under Tezepelumab ^® = is a human monoclonal antibody against TSLP), EDN(eosinophil-derived neurotoxin), nucleolin, annexins.

See below Inflammasome.

DAMPs can be released passively by membrane rupture due to necrosis/necroptosis, although the mechanisms of release appear to differ between the various DAMPs. Other types of cell death such as apoptosis, pyroptosis, ferroptosis and NETosis can also contribute to DAMP release. In addition, some DAMPs can be actively exported from living cells by exocytosis of secretory lysosomes or exosomes, ectosomes and activation of cell membrane channel pores.

DAMPs are recognized by pathogen recognition receptors (see below NOD-like receptors - NLR).

Recognition of DAMPs leads to amplification of an inflammatory response and is involved in beneficial defense responses as well as in harmful immune responses such as autoimmune diseases or autoinflammatory reactions.

Therapeutic use of DAMPs has the potential to provide novel and effective treatments. In developing anti-DAMP strategies, it is important to focus not only on DAMPs as mediators of inflammation, but also to consider the underlying mechanisms of their release from cells and tissues.

1. Castellani JW et al (2015) Cold stress effects on exposure tolerance and exercise performance. Compr Physiol 6:443-469.
2. Murao A et al (2021) Release mechanisms of major DAMPs. Apoptosis 26:152-162.