Table 1.
A list of prominent damage-associated molecular patterns (DAMPs) associated with cell death pathways or extracellular matrix.
| DAMPs | Localization and mode-of-emission | Relevant cell death pathway | Receptors | Reference |
|---|---|---|---|---|
| Annexin A1 | Surface exposed or actively/passively released? | Apoptosis | FPR-1 receptor | (33) |
| Adenosine triphosphate | Actively or passively released | ICD, apoptosis/secondary necrosis and necrosis | P2Y2 and P2×7 | (34–37) |
| B-cell CLL/lymphoma 2 | Passive release | Necrosis | TLR2 | (38) |
| Biglycan | Extracellular matrix | – | TLR2, TLR4, P2×4, and P2×7 | (39, 40) |
| Calreticulin | Mostly surface exposed; sometimes passively released | ICD | CD91 | (35, 41–44) |
| Cardiolipin | Surface exposed? | Apoptosis | ? | (45, 46) |
| Ceramide and sphingosine-1-phosphate | Surface exposed | Apoptosis | ? | (47) |
| Covalent/cross-linked dimer of ribosomal protein S19 | Passively released? | Apoptosis | CD88 | (48–51) |
| Carbamoyl-phosphate synthase 1 | ? | ? | ? | (52) |
| Cyclophilin A | Passive release | Necrosis | CD147 | (53) |
| Cytochrome c | Passively released? | Secondary necrosis and necrosis? | LPG? | (54, 55) |
| Death domain 1α | Surface exposed | Apoptosis | DD1α | (56) |
| Endothelial monocyte-activating polypeptide II | Passively released? | Apoptosis | CXCR3? | (50, 57, 58) |
| F-actin | Passive release | Necrosis | DNGR-1/Clec9a | (59) |
| Fibrinogen | Extracellular matrix | – | TLR4 | (40) |
| Fibronectin extra domain A | Extracellular matrix | – | TLR4? | (40) |
| Fragments of human tyrosyl tRNA synthetase | Passively released? | Apoptosis | ? | (50) |
| Genomic DNA, mRNA, snRNPs | Passive release | Necrosis | TLR3 | (3, 60, 61) |
| GRP78/BiP | Passive release | Necrosis, apoptosis? | ? | (31) |
| H202 | ? | Apoptosis | ? | (62) |
| Heat shock proteins (HSP70, HSP90, HSP60, HSP72, and GP96) | Surface exposure, active secretion, or passive release | ICD, apoptosis/secondary necrosis, necrosis | CD91, TLR2, TLR4, SREC-1 and FEEL-1 | (63–67) |
| Heparan sulfate fragments | Extracellular matrix | – | TLR4 | (40) |
| Hepatoma-derived growth factor | Passively released | Necrosis | ? | (68) |
| Histones | Passively released | Necrosis | TLR-9 | (69) |
| High-mobility group box 1 | Mostly passively released; sometimes actively released | ICD, secondary necrosis and necrosis | TLR2, TLR4, RAGE and TIM3 | (70–73) |
| High-mobility group nucleosome binding domain 1 | Passive release | Necrosis | TLR4 | (74) |
| Hyaluronan | Extracellular matrix | – | TLR2 and TLR4 | (40) |
| IL-1α | Passive release | Necrosis | IL-1R | (75) |
| IL-33 | Passive release | Necrosis | ST2 | (3, 61) |
| IL-6 | Passive release | Necrosis | IL-6R and GP130 | (76) |
| Lysophosphatidylcholine | Passively released? | Apoptosis | G2A | (50, 77) |
| Mit DNA | Passively released | Necrosis | TLR-9 | (78–80) |
| Monosodium urate or uric acid | Passively released | Necrosis | Purinergic receptors | (50, 81) |
| N-formylated peptides | Passively released | Necrosis | FPR-1 | (78, 82–84) |
| Oxidation-associated molecular patterns (reactive protein carbonyls, per-oxidized phospholipids, oxidized low-density lipoprotein) | Passively released | Necrosis, Secondary necrosis | CD36, SR-A, TLR-2/4, CD14 | (85–87) |
| Peroxiredoxin 1 | Actively secreted or passively released | Apoptosis, necrosis | TLR4 | (88) |
| Phosphatidylserine | Actively externalized on the surface | Apoptosis | TIM-1/-3/-4, BAI1, Stabilin-2, MFG-E8, C1q | (56, 89–93) |
| S100/calgranulin protein family members (S100A8, S100A9, S100A12/EN-RAGE) | Passively released | Necrosis | RAGE | (50, 94) |
| Tenascin-C | Extracellular matrix | – | TLR4? | (95) |
| Thrombospondin 1 and its heparin-binding domain | Passively released or surface associated | Apoptosis | αvβ3 integrin | (50, 96) |
| Versican | Extracellular matrix | – | TLR2, TLR6, and CD14 | (40) |
CD, cluster of differentiation; CLEC9A, C-type lectin domain family 9, member A; CPS-1, carbamoyl-phosphate synthase 1, mitochondrial; CXCR3, C-X-C motif receptor 3; FEEL-1/CLEVER-1, fasciclin EGF-like/common lymphatic endothelial and vascular endothelial receptor-1; FPR-1, formyl peptides receptor-1; G2A, G2 accumulation; HMGB1, high-mobility group box 1; HSP, heat shock proteins; ICD, immunogenic cell death; IL, interleukin; LPG, leucine-rich alpha-2-glycoprotein-1; MFG-E8, milk fat globule-egf factor 8 protein; Mit DNA, mitochondrial DNA; P2XR, P2X receptor; P2YR, P2Y receptor; RAGE, receptor for advanced glycation endproducts; SREC-1, scavenger receptor class f member 1; TFAM, mitochondrial transcription factor A; TIM, transmembrane immunoglobulin and mucin domain; TLR, toll-like receptor(s).
Glossary (5, 19, 97): (1) Necrosis: primary necrosis is a form of cell death that can occur in a regulated or accidental manner, characterized by cellular swelling and rapid breakdown of the plasma membrane; (2) Necroptosis: necroptosis is a form of regulated cell death (RCD) manifesting with necrotic morphology and controlled by a signaling cascade involving (among other proteins) RIPK1, RIPK3, and MLKL; (3) Apoptosis: apoptosis is a form of RCD largely dependent on caspases activity and morphologically characterized by cell shrinkage, membrane blebbing, formation of apoptotic bodies, chromatin condensation, and systematic DNA fragmentation; (4) Secondary Necrosis: Secondary necrosis is a terminal process experienced by late-apoptotic cells if they are not cleared by phagocytes in time, and is characterized by general spill-over of apoptotic cellular contents.
“?” Unclear or not determined yet.