Damage-associated molecular pattern

Overview

History

Examples

• Protein DAMPs include intracellular proteins, such as heat-shock proteins or HMGB1, and materials derived from the extracellular matrix that are generated following tissue injury, such as hyaluronan fragments.
• Non-protein DAMPs include ATP, uric acid, heparin sulfate and DNA.

  In humans

Protein DAMPs

1. High-mobility group box 1: HMGB1, a member of the HMG protein family, is a prototypical chromatin-associated LSP, secreted by hematopoietic cells through a lysosome-mediated pathway. HMGB1 is a major mediator of endotoxin shock and is recognized as a DAMP by certain immune cells, triggering an inflammatory response. It is known to induce inflammation by activating NF-κB pathway by binding to TLR, TLR4, TLR9, and RAGE. HMGB1 can also induce dendritic cell maturation via upregulation of CD80, CD83, CD86 and CD11c, and the production of other pro-inflammatory cytokines in myeloid cells, and it can lead to increased expression of cell adhesion molecules on endothelial cells.
2. DNA and RNA: The presence of DNA anywhere other than the nucleus or mitochondria is perceived as a DAMP and triggers responses mediated by TLR9 and DAI that drive cellular activation and immunoreactivity. Some tissues, such as the gut, are inhibited by DNA in their immune response because the gut is filled with trillions of microbiota, which help break down food and regulate the immune system. Without being inhibited by DNA, the gut would detect these microbiota as invading pathogens, and initiate an inflammatory response, which would be detrimental for the organism's health because while the microbiota may be foreign molecules inside the host, they are crucial in promoting host health. Similarly, damaged RNAs released from UVB-exposed keratinocytes activate TLR3 on intact keratinocytes. TLR3 activation stimulates TNF-alpha and IL-6 production, which initiate the cutaneous inflammation associated with sunburn.
3. S100 proteins: S100 is a multigenic family of calcium modulated proteins involved in intracellular and extracellular regulatory activities with a connection to cancer as well as tissue, particularly neuronal, injury. Their main function is the management of calcium storage and shuffling. Although they have various functions, including cell proliferation, differentiation, migration, and energy metabolism, they also act as DAMPs by interacting with their receptors after they are released from phagocytes.
4. Mono- and polysaccharides: The ability of the immune system to recognize hyaluronan fragments is one example of how DAMPs can be made of sugars.

   Nonprotein DAMPs

• Purine metabolites: Nucleotides and nucleosides that have reached the extracellular space can also serve as danger signals by signaling through purinergic receptors. ATP and adenosine are released in high concentrations after catastrophic disruption of the cell, as occurs in necrotic cell death. Extracellular ATP triggers mast cell degranulation by signaling through P2X7 receptors. Similarly, adenosine triggers degranulation through P1 receptors. Uric acid is also an endogenous danger signal released by injured cells. Adenosine triphosphate and uric acid, which are purine metabolites, activate NLR family, pyrin domain containing 3 inflammasomes to induce IL-1β and IL-18.

  In plants