{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:47:03Z","timestamp":1781113623518,"version":"3.54.1"},"reference-count":59,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X007243\/1"],"award-info":[{"award-number":["MR\/X007243\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR Surgical Reconstruction and Microbiology Research Centre (NIHR-SRMRC)","award":["MR\/X007243\/1"],"award-info":[{"award-number":["MR\/X007243\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Traumatic injury leads to an extension of the half-life of circulating neutrophils. However, how quickly neutrophil apoptosis is delayed post-injury is currently unknown, as are the underlying mechanisms and factors that promote this extension of lifespan. During the ultra-early (\u22641 h) and acute (4\u201312 and 48\u201372 h) post-injury phases, we collected blood samples from 73 adult trauma patients. Following ex vivo culture, neutrophil apoptosis was measured, alongside caspase-3 activation and expression of the anti-apoptotic protein Mcl-1. To identify factors that may promote neutrophil survival post-trauma, neutrophils from healthy controls (HCs) were cultured with mitochondrial-derived damage-associated molecular patterns (mtDAMPs) or mitochondrial DNA (mtDNA). Accompanied by reduced mitochondrial membrane depolarisation, delayed Mcl-1 turnover, and reduced caspase-3 activation, the ex vivo lifespan of neutrophils from trauma patients was significantly enhanced in a protein synthesis-independent manner within minutes to hours after injury. Neutrophils from HCs exhibited delayed apoptosis when cultured in media supplemented with trauma patient serum, which occurred alongside stabilisation of Mcl-1. Culturing HCs neutrophils with mtDAMPs or mtDNA significantly delayed apoptosis rates, promoted stabilisation of Mcl-1, and reduced caspase-3 activation. The release of mtDAMPs from damaged tissue may drive post-trauma immune dysregulation by promoting the survival of dysfunctional neutrophils.<\/jats:p>","DOI":"10.3390\/cells14100754","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T09:58:22Z","timestamp":1747821502000},"page":"754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Major Traumatic Injury and Exposure to Mitochondrial-Derived Damage-Associated Molecular Patterns Promotes Neutrophil Survival Accompanied by Stabilisation of the Anti-Apoptotic Protein Mcl-1"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5826-7312","authenticated-orcid":false,"given":"Thomas","family":"Nicholson","sequence":"first","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Macleod","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3211-9933","authenticated-orcid":false,"given":"Antonio","family":"Belli","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet M.","family":"Lord","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TT, UK"},{"name":"MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Hazeldine","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"260","DOI":"10.5492\/wjccm.v10.i5.260","article-title":"Neutrophil kinetics and function after major trauma: A systematic review","volume":"10","author":"Finlay","year":"2021","journal-title":"World J. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1097\/00005373-199509000-00003","article-title":"Early neutrophil sequestration after injury: A pathogenic mechanism for multiple organ failure","volume":"39","author":"Botha","year":"1995","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1097\/00003246-200208000-00007","article-title":"Increased neutrophil migratory activity after major trauma: A factor in the etiology of acute respiratory distress syndrome?","volume":"30","author":"Pallister","year":"2002","journal-title":"Crit. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1097\/SLA.0000000000001807","article-title":"Neutrophil Dysfunction, Immature Granulocytes, and Cell-free DNA are Early Biomarkers of Sepsis in Burn-injured Patients: A Prospective Observational Cohort Study","volume":"265","author":"Hampson","year":"2017","journal-title":"Ann. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1097\/SHK.0000000000001695","article-title":"Neutrophil Phenotypes and Functions in Trauma and Trauma-Related Sepsis","volume":"56","author":"Janicova","year":"2021","journal-title":"Shock"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Jones, C.N., Moore, M., Dimisko, L., Alexander, A., Ibrahim, A., Hassell, B.A., Warren, H.S., Tompkins, R.G., Fagan, S.P., and Irimia, D. (2014). Spontaneous neutrophil migration patterns during sepsis after major burns. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114509"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Liao, Y., Liu, P., Guo, F., Zhang, Z.Y., and Zhang, Z. (2013). Oxidative burst of circulating neutrophils following traumatic brain injury in human. PLoS ONE, 8.","DOI":"10.1371\/annotation\/73ce45d3-4478-4c06-a4d2-3274b6222bae"},{"key":"ref_8","first-page":"1208","article-title":"Mechanism of delayed apoptosis of peripheral blood neutrophils in severely burned patients","volume":"31","author":"Qi","year":"2019","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1007\/s001340050365","article-title":"Base deficit after major trauma directly relates to neutrophil CD11b expression: A proposed mechanism of shock-induced organ injury","volume":"23","author":"Botha","year":"1997","journal-title":"Intensive Care Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.injury.2008.11.002","article-title":"Modulation of the innate immune response after trauma visualised by a change in functional PMN phenotype","volume":"40","author":"Hietbrink","year":"2009","journal-title":"Injury"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Laggner, M., Lingitz, M.-T., Copic, D., Direder, M., Klas, K., Bormann, D., Gugerell, A., Moser, B., Radtke, C., and Hacker, S. (2022). Severity of thermal burn injury is associated with systemic neutrophil activation. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-05768-w"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hazeldine, J., Naumann, D.N., Toman, E., Davies, D., Bishop, J.R.B., Su, Z., Hampson, P., Dinsdale, R.J., Crombie, N., and Duggal, N.A. (2017). Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: A prospective cohort study. PLoS Med., 14.","DOI":"10.1371\/journal.pmed.1002338"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/SHK.0b013e318295a40a","article-title":"Kinetics of the innate immune response after trauma: Implications for the development of late onset sepsis","volume":"40","author":"Hietbrink","year":"2013","journal-title":"Shock"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1016\/j.burns.2021.02.004","article-title":"Investigation and assessment of neutrophil dysfunction early after severe burn injury","volume":"47","author":"Yang","year":"2021","journal-title":"Burns"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S0039-6060(99)70155-8","article-title":"Neutrophils are primed for cytotoxicity and resist apoptosis in injured patients at risk for multiple organ failure","volume":"126","author":"Biffl","year":"1999","journal-title":"Surgery"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"325","DOI":"10.2119\/molmed.2011.00380","article-title":"Molecular mechanisms underlying delayed apoptosis in neutrophils from multiple trauma patients with and without sepsis","volume":"18","author":"Kirichevska","year":"2012","journal-title":"Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1097\/00005373-200004000-00004","article-title":"Inhibition of neutrophil apoptosis after severe trauma is NFkappabeta dependent","volume":"48","author":"Nolan","year":"2000","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"R20","DOI":"10.1186\/cc9965","article-title":"Increased serum soluble Fas after major trauma is associated with delayed neutrophil apoptosis and development of sepsis","volume":"15","author":"Scholz","year":"2011","journal-title":"Crit. Care"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ehrnthaller, C., Braum\u00fcller, S., Kellermann, S., Gebhard, F., Perl, M., and Huber-Lang, M. (2021). Complement Factor C5a Inhibits Apoptosis of Neutrophils-A Mechanism in Polytrauma?. J. Clin. Med., 10.","DOI":"10.3390\/jcm10143157"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1097\/SHK.0000000000000038","article-title":"Prehospital hypertonic saline resuscitation attenuates the activation and promotes apoptosis of neutrophils in patients with severe traumatic brain injury","volume":"40","author":"Junger","year":"2013","journal-title":"Shock"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6198","DOI":"10.4049\/jimmunol.0901264","article-title":"Mcl-1-mediated impairment of the intrinsic apoptosis pathway in circulating neutrophils from critically ill patients can be overcome by Fas stimulation","volume":"183","author":"Altrichter","year":"2009","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1002\/jlb.59.6.835","article-title":"Inhibition of apoptosis in polymorphonuclear neutrophils from burn patients","volume":"59","author":"Chitnis","year":"1996","journal-title":"J. Leukoc. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1189\/jlb.3A1114-537RR","article-title":"Staurosporine resistance in inflammatory neutrophils is associated with the inhibition of caspase- and proteasome-mediated Mcl-1 degradation","volume":"99","author":"Hornstein","year":"2016","journal-title":"J. Leukoc. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41580-018-0089-8","article-title":"Regulation of apoptosis in health and disease: The balancing act of BCL-2 family proteins","volume":"20","author":"Singh","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1146\/annurev-immunol-042617-053010","article-title":"Apoptosis and Clearance of Apoptotic Cells","volume":"36","author":"Nagata","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1100\/2011\/131539","article-title":"Regulation of neutrophil survival\/apoptosis by Mcl-1","volume":"11","author":"Milot","year":"2011","journal-title":"Sci. World J."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tantawy, S.I., Timofeeva, N., Sarkar, A., and Gandhi, V. (2023). Targeting MCL-1 protein to treat cancer: Opportunities and challenges. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1226289"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/s41418-019-0486-3","article-title":"Saga of Mcl-1: Regulation from transcription to degradation","volume":"27","author":"Senichkin","year":"2020","journal-title":"Cell Death Differ."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1100\/tsw.2010.169","article-title":"Role of neutrophil apoptosis in the resolution of inflammation","volume":"10","author":"Filep","year":"2010","journal-title":"Sci. World J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"C170","DOI":"10.1152\/ajpcell.00187.2003","article-title":"Suppression of mitochondria-dependent neutrophil apoptosis with thermal injury","volume":"286","author":"Hu","year":"2004","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1089\/10962960152813322","article-title":"Neutrophil apoptosis is delayed by trauma patients\u2019 plasma via a mechanism involving proinflammatory phospholipids protein kinase C","volume":"2","author":"Biffl","year":"2001","journal-title":"Surg. Infect."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sarabhai, T., Peter, C., B\u00e4r, A.-K., Windolf, J., Relja, B., Wesselborg, S., Wahlers, T., and Paunel-G\u00f6rg\u00fcl\u00fc, A. (2017). Serum \u03b1-1 Antitrypsin (AAT) antagonizes intrinsic apoptosis induction in neutrophils from patients with systemic inflammatory response syndrome. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177450"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hazeldine, J., Dinsdale, R.J., Harrison, P., and Lord, J.M. (2019). Traumatic Injury and Exposure to Mitochondrial-Derived Damage Associated Molecular Patterns Suppresses Neutrophil Extracellular Trap Formation. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00685"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1097\/TA.0000000000001971","article-title":"A subset of five human mitochondrial formyl peptides mimics bacterial peptides and functionally deactivates human neutrophils","volume":"85","author":"Kaczmarek","year":"2018","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1373\/clinchem.2003.025783","article-title":"Plasma mitochondrial DNA concentrations after trauma","volume":"50","author":"Lam","year":"2004","journal-title":"Clin. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1133.e1","DOI":"10.1016\/j.jcrc.2014.07.013","article-title":"Mitochondrial DNA neutrophil extracellular traps are formed after trauma and subsequent surgery","volume":"29","author":"McIlroy","year":"2014","journal-title":"J. Crit. Care"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1097\/SHK.0000000000000397","article-title":"Comparison of the Proinflammatory and Procoagulant Properties of Nuclear, Mitochondrial, and Bacterial DNA","volume":"44","author":"Bhagirath","year":"2015","journal-title":"Shock"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.injury.2015.03.028","article-title":"N-Formyl peptides drive mitochondrial damage associated molecular pattern induced neutrophil activation through ERK1\/2 and P38 MAP kinase signalling pathways","volume":"46","author":"Hazeldine","year":"2015","journal-title":"Injury"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1189\/jlb.70.6.881","article-title":"Senescence in innate immune responses: Reduced neutrophil phagocytic capacity and CD16 expression in elderly humans","volume":"70","author":"Butcher","year":"2001","journal-title":"J. Leukoc. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.4049\/jimmunol.153.3.1254","article-title":"Neutrophil apoptosis is associated with a reduction in CD16 (Fc gamma RIII) expression","volume":"153","author":"Dransfield","year":"1994","journal-title":"J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wardle, D.J., Burgon, J., Sabroe, I., Bingle, C.D., Whyte, M.K.B., and Renshaw, S.A. (2011). Effective caspase inhibition blocks neutrophil apoptosis and reveals Mcl-1 as both a regulator and a target of neutrophil caspase activation. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0015768"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1097\/TA.0000000000000509","article-title":"Mitochondrial damage-associated molecular patterns from fractures suppress pulmonary immune responses via formyl peptide receptors 1 and 2","volume":"78","author":"Li","year":"2015","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1097\/SHK.0b013e3181cd8c08","article-title":"Mitochondrial DNA is released by shock and activates neutrophils via p38 map kinase","volume":"34","author":"Zhang","year":"2010","journal-title":"Shock"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Itagaki, K., Kaczmarek, E., Lee, Y.T., Tang, I.T., Isal, B., Adibnia, Y., Sandler, N., Grimm, M.J., Segal, B.H., and Otterbein, L.E. (2015). Mitochondrial DNA released by trauma induces neutrophil extracellular traps. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120549"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"88","DOI":"10.2119\/molmed.2010.00080","article-title":"Interleukin-18 delays neutrophil apoptosis following alcohol intoxication and burn injury","volume":"17","author":"Akhtar","year":"2011","journal-title":"Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1182\/blood.V92.7.2495","article-title":"Mcl-1 expression in human neutrophils: Regulation by cytokines and correlation with cell survival","volume":"92","author":"Moulding","year":"1998","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"C1171","DOI":"10.1152\/ajpcell.00312.2004","article-title":"Activation of PI3-kinase\/PKB contributes to delay in neutrophil apoptosis after thermal injury","volume":"288","author":"Hu","year":"2005","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature08780","article-title":"Circulating mitochondrial DAMPs cause inflammatory responses to injury","volume":"464","author":"Zhang","year":"2010","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1189\/jlb.0605289","article-title":"Spontaneous neutrophil apoptosis and regulation of cell survival by granulocyte macrophage-colony stimulating factor","volume":"78","author":"Kobayashi","year":"2005","journal-title":"J. Leukoc. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1097\/SHK.0000000000001969","article-title":"Not all cell-free mitochondrial DNA is equal in trauma patients","volume":"58","author":"Briggs","year":"2022","journal-title":"Shock"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1097\/SLA.0b013e3182a4ea46","article-title":"Elevated levels of plasma mitochondrial DNA DAMPs are linked to clinical outcome in severely injured human subjects","volume":"258","author":"Simmons","year":"2013","journal-title":"Ann. Surg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.chest.2019.09.028","article-title":"Plasma Mitochondrial DNA Levels Are Associated With ARDS in Trauma and Sepsis Patients","volume":"157","author":"Faust","year":"2020","journal-title":"Chest"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/S0898-6568(01)00151-6","article-title":"Role of extracellular signal-regulated kinase and phosphatidylinositol-3 kinase in chemoattractant and LPS delay of constitutive neutrophil apoptosis","volume":"13","author":"Klein","year":"2001","journal-title":"Cell Signal."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8544","DOI":"10.4049\/jimmunol.179.12.8544","article-title":"Inhibition of neutrophil apoptosis by ATP is mediated by the P2Y11 receptor","volume":"179","author":"Vaughan","year":"2007","journal-title":"J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s10495-013-0948-x","article-title":"Extracellular NAD(+) inhibits human neutrophil apoptosis","volume":"19","author":"Pliyev","year":"2014","journal-title":"Apoptosis"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e1102","DOI":"10.1038\/cddis.2014.70","article-title":"Extracellular ATP drives systemic inflammation, tissue damage and mortality","volume":"5","author":"Cauwels","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1089\/neu.2020.7226","article-title":"In Vivo Detection of Extracellular Adenosine Triphosphate in a Mouse Model of Traumatic Brain Injury","volume":"38","author":"Faroqi","year":"2021","journal-title":"J. Neurotrauma"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"101608","DOI":"10.1016\/j.bonr.2022.101608","article-title":"Extracellular ATP and its derivatives provide spatiotemporal guidance for bone adaptation to wide spectrum of physical forces","volume":"17","author":"Dsouza","year":"2022","journal-title":"Bone Rep."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Horner, E., Lord, J.M., and Hazeldine, J. (2023). The immune suppressive properties of damage associated molecular patterns in the setting of sterile traumatic injury. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1239683"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/10\/754\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:36:35Z","timestamp":1760031395000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/10\/754"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,21]]},"references-count":59,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["cells14100754"],"URL":"https:\/\/doi.org\/10.3390\/cells14100754","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,21]]}}}