Damage-associated molecular pattern

Damage-associated molecular patterns (DAMPs)^[1] are molecules within cells that are a component of the innate immune response released from damaged or dying cells due to trauma or an infection by a pathogen.^[2] They are also known as danger signals, and alarmins because they serve as warning signs to alert the organism to any damage or infection to its cells. DAMPs are endogenous danger signals that are discharged to the extracellular space in response to damage to the cell from mechanical trauma or a pathogen.^[3] Once a DAMP is released from the cell, it promotes a noninfectious inflammatory response by binding to a pattern recognition receptor (PRR).^[4] Inflammation is a key aspect of the innate immune response; it is used to help mitigate future damage to the organism by removing harmful invaders from the affected area and start the healing process.^[5] As an example, the cytokine IL-1α is a DAMP that originates within the nucleus of the cell which, once released to the extracellular space, binds to the PRR IL-1R, which in turn initiates an inflammatory response to the trauma or pathogen that initiated the release of IL-1α.^[3] In contrast to the noninfectious inflammatory response produced by DAMPs, pathogen-associated molecular patterns (PAMPs) initiate and perpetuate the infectious pathogen-induced inflammatory response.^[6] Many DAMPs are nuclear or cytosolic proteins with defined intracellular function that are released outside the cell following tissue injury.^[7] This displacement from the intracellular space to the extracellular space moves the DAMPs from a reducing to an oxidizing environment, causing their functional denaturation, resulting in their loss of function.^[7] Outside of the aforementioned nuclear and cytosolic DAMPs, there are other DAMPs originated from different sources, such as mitochondria, granules, the extracellular matrix, the endoplasmic reticulum, and the plasma membrane.^[3]