{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:43:31Z","timestamp":1785321811978,"version":"3.55.0"},"reference-count":74,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"US government, including National Institutes of Health","award":["R01 AI119965"],"award-info":[{"award-number":["R01 AI119965"]}]},{"DOI":"10.13039\/100018719","name":"University of Missouri School of Medicine","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100018719","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Human neutrophils are abundant, short-lived leukocytes that turn over at a rate of approximately 10<jats:sup>11<\/jats:sup> cells\/day via a constitutive apoptosis program. Certain growth factors, inflammatory mediators and infectious agents can delay apoptosis or induce neutrophils to die by other mechanisms. Nonetheless, a large body of data demonstrates that apoptosis of untreated neutrophils typically ensues within 24 hours of cell isolation and <jats:italic>in vitro<\/jats:italic> culture. At the molecular level apoptosis is driven by executioner caspase-3, and during this process cell proinflammatory capacity and host defense functions are downregulated. We undertook the current study to determine the extent to which human neutrophil viability and function could be prolonged by treatment with the non-toxic, irreversible, pan-caspase inhibitor Q-VD-OPh. Our data demonstrate that a single 10 \u03bcM dose of this drug was sufficient to markedly prolong cell lifespan. Specifically, we show that apoptosis was prevented for at least 5 days as indicated by analysis of nuclear morphology, DNA fragmentation, and phosphatidylserine externalization together with measurements of procaspase-3 processing and caspase activity. Conversely, mitochondrial depolarization declined despite abundant Myeloid Cell Leukemia 1 (MCL-1). At the same time, glutathione levels were maintained and Q-VD-OPh prevented age-associated increases mitochondrial oxidative stress. Regarding functional capacity, we show that phagocytosis, NADPH oxidase activity, chemotaxis, and degranulation were maintained following Q-VD-OPh treatment, albeit to somewhat different extents. Thus, a single 10 \u03bcM dose of Q-VD-OPh can sustain human neutrophil viability and function for at least 5 days.<\/jats:p>","DOI":"10.1371\/journal.pone.0316912","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T18:27:21Z","timestamp":1736274441000},"page":"e0316912","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of the pan-caspase inhibitor Q-VD-OPh on human neutrophil lifespan and function"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6511-7814","authenticated-orcid":true,"given":"Lisa","family":"Khuu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisha","family":"Pillay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Prichard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8929-6968","authenticated-orcid":true,"given":"Lee-Ann H.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"pone.0316912.ref001","doi-asserted-by":"crossref","first-page":"15","DOI":"10.4137\/JCD.S11038","article-title":"Regulation of human neutrophil apoptosis and lifespan in health and disease","volume":"7","author":"JM McCracken","year":"2014","journal-title":"J Cell Death"},{"key":"pone.0316912.ref002","doi-asserted-by":"crossref","first-page":"631821","DOI":"10.3389\/fimmu.2021.631821","article-title":"Neutrophils: Many Ways to Die","volume":"12","author":"E Perez-Figueroa","year":"2021","journal-title":"Front Immunol"},{"issue":"1\u20133","key":"pone.0316912.ref003","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s12026-008-8049-6","article-title":"Neutrophil apoptosis and the resolution of infection","volume":"43","author":"AD Kennedy","year":"2009","journal-title":"Immunol Res"},{"issue":"3","key":"pone.0316912.ref004","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1172\/JCI113970","article-title":"Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages","volume":"83","author":"JS Savill","year":"1989","journal-title":"J Clin Invest"},{"issue":"11","key":"pone.0316912.ref005","doi-asserted-by":"crossref","first-page":"5124","DOI":"10.4049\/jimmunol.150.11.5124","article-title":"Impairment of function in aging neutrophils is associated with apoptosis","volume":"150","author":"MK Whyte","year":"1993","journal-title":"J Immunol"},{"issue":"4","key":"pone.0316912.ref006","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1189\/jlb.1112571","article-title":"What\u2019s your age again? Determination of human neutrophil half-lives revisited","volume":"94","author":"T Tak","year":"2013","journal-title":"J Leukoc Biol"},{"issue":"6","key":"pone.0316912.ref007","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":"SD Kobayashi","year":"2005","journal-title":"J Leukoc Biol"},{"issue":"7","key":"pone.0316912.ref008","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.4049\/jimmunol.1102863","article-title":"Francisella tularensis inhibits the intrinsic and extrinsic pathways to delay constitutive apoptosis and prolong human neutrophil lifespan","volume":"188","author":"JT Schwartz","year":"2012","journal-title":"J Immunol"},{"issue":"11","key":"pone.0316912.ref009","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1007\/s00018-019-03060-1","article-title":"Neutrophil pyroptosis: new perspectives on sepsis","volume":"76","author":"L Liu","year":"2019","journal-title":"Cell Mol Life Sci"},{"key":"pone.0316912.ref010","doi-asserted-by":"crossref","first-page":"107233","DOI":"10.1016\/j.intimp.2020.107233","article-title":"Neutrophils and COVID-19: The road so far","volume":"90","author":"LHA Cavalcante-Silva","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"pone.0316912.ref011","doi-asserted-by":"crossref","first-page":"237","DOI":"10.3389\/fcimb.2020.00237","article-title":"Identification of the PANoptosome: A Molecular Platform Triggering Pyroptosis, Apoptosis, and Necroptosis (PANoptosis)","volume":"10","author":"S Christgen","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"issue":"5","key":"pone.0316912.ref012","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1182\/blood-2008-04-149575","article-title":"Granulocyte colony-stimulating factor delays neutrophil apoptosis by inhibition of calpains upstream of caspase-3","volume":"112","author":"BJ van Raam","year":"2008","journal-title":"Blood"},{"issue":"8","key":"pone.0316912.ref013","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1182\/blood.V80.8.2012.2012","article-title":"Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products","volume":"80","author":"F Colotta","year":"1992","journal-title":"Blood"},{"issue":"2","key":"pone.0316912.ref014","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/sj.cdd.4402044","article-title":"Broad-spectrum caspase inhibitors: from myth to reality?","volume":"14","author":"D Chauvier","year":"2007","journal-title":"Cell Death Differ"},{"issue":"11","key":"pone.0316912.ref015","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1002\/jcb.23263","article-title":"Dose-dependent effects of the caspase inhibitor Q-VD-OPh on different apoptosis-related processes","volume":"112","author":"K Kuzelova","year":"2011","journal-title":"J Cell Biochem"},{"issue":"1","key":"pone.0316912.ref016","doi-asserted-by":"crossref","first-page":"e15768","DOI":"10.1371\/journal.pone.0015768","article-title":"Effective caspase inhibition blocks neutrophil apoptosis and reveals Mcl-1 as both a regulator and a target of neutrophil caspase activation","volume":"6","author":"DJ Wardle","year":"2011","journal-title":"PLoS One"},{"issue":"4","key":"pone.0316912.ref017","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1023\/A:1024116916932","article-title":"Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties","volume":"8","author":"TM Caserta","year":"2003","journal-title":"Apoptosis"},{"key":"pone.0316912.ref018","doi-asserted-by":"crossref","first-page":"836754","DOI":"10.3389\/fimmu.2022.836754","article-title":"Metabolic Reprogramming Mediates Delayed Apoptosis of Human Neutrophils Infected With Francisella tularensis","volume":"13","author":"SJ Krysa","year":"2022","journal-title":"Front Immunol"},{"key":"pone.0316912.ref019","doi-asserted-by":"crossref","first-page":"532","DOI":"10.3389\/fimmu.2020.00532","article-title":"An Attempt to Polarize Human Neutrophils Toward N1 and N2 Phenotypes in vitro","volume":"11","author":"M Ohms","year":"2020","journal-title":"Front Immunol"},{"key":"pone.0316912.ref020","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-1-0716-0154-9_3","article-title":"Isolation of Human Neutrophils from Venous Blood","volume":"2087","author":"S Kremserova","year":"2020","journal-title":"Methods Mol Biol"},{"issue":"3","key":"pone.0316912.ref021","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1159\/000443882","article-title":"Francisella tularensis Modulates a Distinct Subset of Regulatory Factors and Sustains Mitochondrial Integrity to Impair Human Neutrophil Apoptosis","volume":"8","author":"JM McCracken","year":"2016","journal-title":"J Innate Immun"},{"key":"pone.0316912.ref022","doi-asserted-by":"crossref","first-page":"653100","DOI":"10.3389\/fimmu.2021.653100","article-title":"Microtubules and Dynein Regulate Human Neutrophil Nuclear Volume and Hypersegmentation During H. pylori Infection","volume":"12","author":"SL Silva-Del Toro","year":"2021","journal-title":"Front Immunol"},{"key":"pone.0316912.ref023","doi-asserted-by":"crossref","first-page":"1038349","DOI":"10.3389\/fimmu.2022.1038349","article-title":"Helicobacter pylori-infected human neutrophils exhibit impaired chemotaxis and a uropod retraction defect","volume":"13","author":"A Prichard","year":"2022","journal-title":"Front Immunol"},{"issue":"11","key":"pone.0316912.ref024","doi-asserted-by":"crossref","first-page":"e430","DOI":"10.1038\/cddis.2012.171","article-title":"JC-1: alternative excitation wavelengths facilitate mitochondrial membrane potential cytometry","volume":"3","author":"A Perelman","year":"2012","journal-title":"Cell Death Dis"},{"key":"pone.0316912.ref025","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/978-1-62703-845-4_16","article-title":"Immunofluorescence and confocal microscopy of neutrophils","volume":"1124","author":"L-AH Allen","year":"2014","journal-title":"Methods Mol Biol"},{"issue":"49","key":"pone.0316912.ref026","doi-asserted-by":"crossref","first-page":"34315","DOI":"10.1074\/jbc.M803141200","article-title":"ClC-3 and IClswell are required for normal neutrophil chemotaxis and shape change","volume":"283","author":"AP Volk","year":"2008","journal-title":"J Biol Chem"},{"issue":"2","key":"pone.0316912.ref027","doi-asserted-by":"crossref","DOI":"10.1111\/cmi.12795","article-title":"Bacterial lipoproteins and other factors released by Francisella tularensis modulate human neutrophil lifespan: Effects of a TLR1 SNP on apoptosis inhibition","volume":"20","author":"LC Kinkead","year":"2018","journal-title":"Cell Microbiol"},{"issue":"6","key":"pone.0316912.ref028","doi-asserted-by":"crossref","first-page":"3658","DOI":"10.4049\/jimmunol.174.6.3658","article-title":"Helicobacter pylori disrupts NADPH oxidase targeting in human neutrophils to induce extracellular superoxide release","volume":"174","author":"L-AH Allen","year":"2005","journal-title":"J Immunol"},{"key":"pone.0316912.ref029","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4137\/JCD.S23844","article-title":"Inhibition of Apoptosis and Efficacy of Pan Caspase Inhibitor, Q-VD-OPh, in Models of Human Disease","volume":"8","author":"CL Keoni","year":"2015","journal-title":"J Cell Death"},{"issue":"2","key":"pone.0316912.ref030","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/sj.cdd.4401320","article-title":"Functional characterization of mitochondria in neutrophils: a role restricted to apoptosis","volume":"11","author":"NA Maianski","year":"2004","journal-title":"Cell Death Differ"},{"issue":"9","key":"pone.0316912.ref031","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1038\/cdd.2011.75","article-title":"Peculiarities of cell death mechanisms in neutrophils","volume":"18","author":"B Geering","year":"2011","journal-title":"Cell Death Differ"},{"issue":"2","key":"pone.0316912.ref032","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1159\/000342430","article-title":"Francisella tularensis alters human neutrophil gene expression: insights into the molecular basis of delayed neutrophil apoptosis","volume":"5","author":"JT Schwartz","year":"2013","journal-title":"J Innate Immun"},{"key":"pone.0316912.ref033","doi-asserted-by":"crossref","first-page":"1075751","DOI":"10.3389\/fcell.2022.1075751","article-title":"Making the head: Caspases in life and death","volume":"10","author":"E Svandova","year":"2022","journal-title":"Front Cell Dev Biol"},{"issue":"5","key":"pone.0316912.ref034","doi-asserted-by":"crossref","first-page":"e19786","DOI":"10.1371\/journal.pone.0019786","article-title":"Caspase inhibition blocks cell death and enhances mitophagy but fails to promote T-cell lymphoma","volume":"6","author":"SH Wang","year":"2011","journal-title":"PLoS One"},{"key":"pone.0316912.ref035","doi-asserted-by":"crossref","first-page":"467","DOI":"10.3389\/fcell.2020.00467","article-title":"Mitophagy, Mitochondrial Homeostasis, and Cell Fate","volume":"8","author":"K Ma","year":"2020","journal-title":"Front Cell Dev Biol"},{"issue":"18","key":"pone.0316912.ref036","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1177\/15353702231191178","article-title":"Metformin inhibits mitochondrial dysfunction and apoptosis in cardiomyocytes induced by high glucose via upregulating AMPK activity","volume":"248","author":"Y. Wu","year":"2023","journal-title":"Exp Biol Med (Maywood)"},{"issue":"Oct 25","key":"pone.0316912.ref037","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.2147\/DDDT.S428024","article-title":"Dexmedetomidine ameliorates cardiac ischemia reperfusion injury by enhancing autophagy through activation of the AMPK\/SIRT3 pathway","volume":"17","author":"H He","year":"2023","journal-title":"Drug Des Devel Ther"},{"issue":"2","key":"pone.0316912.ref038","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1177\/153537020623100209","article-title":"Redox state and superoxide production in neutrophils of Crohn\u2019s disease patients","volume":"231","author":"C Biagioni","year":"2006","journal-title":"Exp Biol Med"},{"issue":"1","key":"pone.0316912.ref039","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1177\/1753425920951985","article-title":"Metabolomic analysis of spontaneous neutrophil apoptosis reveals the potential involvement of glutathione depletion","volume":"27","author":"X Yuyun","year":"2021","journal-title":"Innate Immun"},{"issue":"2","key":"pone.0316912.ref040","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1007\/s10753-017-0725-z","article-title":"Changes in Neutrophil Metabolism upon Activation and Aging","volume":"41","author":"BC Richer","year":"2018","journal-title":"Inflammation"},{"key":"pone.0316912.ref041","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.freeradbiomed.2020.09.022","article-title":"Protein kinase C activates NAD kinase in human neutrophils","volume":"161","author":"R Rabani","year":"2020","journal-title":"Free Radic Biol Med"},{"issue":"6","key":"pone.0316912.ref042","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1189\/jlb.0406287","article-title":"Pivotal Advance: Francisella tularensis LVS evades killing by human neutrophils via inhibition of the respiratory burst and phagosome escape","volume":"80","author":"RL McCaffrey","year":"2006","journal-title":"J Leukoc Biol"},{"issue":"12","key":"pone.0316912.ref043","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/nchembio.116","article-title":"CD15 expression in human myeloid cell differentiation is regulated by sialidase activity","volume":"4","author":"SZ Gadhoum","year":"2008","journal-title":"Nat Chem Biol"},{"issue":"5","key":"pone.0316912.ref044","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.4049\/jimmunol.1601292","article-title":"Cutting Edge: Helicobacter pylori Induces Nuclear Hypersegmentation and Subtype Differentiation of Human Neutrophils In Vitro","volume":"198","author":"LC Whitmore","year":"2017","journal-title":"J Immunol"},{"issue":"4","key":"pone.0316912.ref045","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1002\/eji.200535257","article-title":"ADAM17 activity during human neutrophil activation and apoptosis","volume":"36","author":"B Walcheck","year":"2006","journal-title":"Eur J Immunol"},{"issue":"7","key":"pone.0316912.ref046","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1182\/blood-2006-02-005827","article-title":"ADAM17 deficiency by mature neutrophils has differential effects on L-selectin shedding","volume":"108","author":"Y Li","year":"2006","journal-title":"Blood"},{"issue":"11","key":"pone.0316912.ref047","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1182\/blood.V78.11.3030.3030","article-title":"Intracellular localization of glycosyl-phosphatidylinositol-anchored CD67 and FcRIII (CD16) in affected neutrophil granulocytes of patients with paroxysmal nocturnal hemoglobinuria","volume":"78","author":"CR Jost","year":"1991","journal-title":"Blood"},{"issue":"11","key":"pone.0316912.ref048","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1182\/blood.V85.11.3264.bloodjournal85113264","article-title":"Regulation of cell adhesion molecule expression and function associated with neutrophil apoptosis","volume":"85","author":"I Dransfield","year":"1995","journal-title":"Blood"},{"issue":"2\u20133","key":"pone.0316912.ref049","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.molimm.2009.09.018","article-title":"Complement receptor 3, not Dectin-1, is the major receptor on human neutrophils for beta-glucan-bearing particles","volume":"47","author":"R van Bruggen","year":"2009","journal-title":"Mol Immunol"},{"issue":"11","key":"pone.0316912.ref050","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1016\/j.celrep.2015.08.019","article-title":"Autophagy Is Required for Neutrophil-Mediated Inflammation","volume":"12","author":"A Bhattacharya","year":"2015","journal-title":"Cell Rep"},{"key":"pone.0316912.ref051","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.pneurobio.2013.10.004","article-title":"Autophagy and apoptosis dysfunction in neurodegenerative disorders","volume":"112","author":"S Ghavami","year":"2014","journal-title":"Prog Neurobiol"},{"issue":"10","key":"pone.0316912.ref052","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/s41419-023-06154-8","article-title":"Autophagy: Regulator of cell death","volume":"14","author":"S Liu","year":"2023","journal-title":"Cell Death Dis"},{"issue":"1","key":"pone.0316912.ref053","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00726-008-0230-7","article-title":"mTOR phosphorylated at S2448 binds to raptor and rictor","volume":"38","author":"M Rosner","year":"2010","journal-title":"Amino Acids"},{"issue":"3","key":"pone.0316912.ref054","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41580-022-00542-2","article-title":"The mechanisms and roles of selective autophagy in mammals","volume":"24","author":"JNS Vargas","year":"2023","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"1","key":"pone.0316912.ref055","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1348-0421.2010.00271.x","article-title":"Autophagy basics","volume":"55","author":"I. Tanida","year":"2011","journal-title":"Microbiol Immunol"},{"issue":"2","key":"pone.0316912.ref056","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1177\/153537020623100209","article-title":"REdox state and O2- production in neutrophils of Crohh\u2019s disease patients","volume":"231","author":"C Biagioni","year":"2006","journal-title":"Exp Biol"},{"key":"pone.0316912.ref057","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.3389\/fimmu.2019.02099","article-title":"Metabolic Insight of Neutrophils in Health and Disease","volume":"10","author":"S Kumar","year":"2019","journal-title":"Front Immunol"},{"issue":"4","key":"pone.0316912.ref058","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/sj.cdd.4401360","article-title":"Catalytic activity of caspase-3 is required for its degradation: stabilization of the active complex by synthetic inhibitors","volume":"11","author":"P Tawa","year":"2004","journal-title":"Cell Death Differ"},{"issue":"July 7","key":"pone.0316912.ref059","doi-asserted-by":"crossref","first-page":"eabe9887","DOI":"10.1126\/scitranslmed.abe9887","article-title":"Pan-caspase inhibition as a potential host-directed immunotherapy against MRSA and other bacterial skin infections","volume":"13","author":"MP Alphonse","year":"2021","journal-title":"Sci Transl Med"},{"issue":"10","key":"pone.0316912.ref060","doi-asserted-by":"crossref","first-page":"e2422","DOI":"10.1038\/cddis.2016.311","article-title":"Loss of XIAP facilitates switch to TNFalpha-induced necroptosis in mouse neutrophils","volume":"7","author":"S Wicki","year":"2016","journal-title":"Cell Death Dis"},{"key":"pone.0316912.ref061","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.12688\/f1000research.16439.1","article-title":"Recent advances in understanding inhibitor of apoptosis proteins","volume":"7","author":"N Lalaoui","year":"2018","journal-title":"F1000 Res"},{"issue":"1","key":"pone.0316912.ref062","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jhep.2014.08.023","article-title":"Increased autophagy sustains the survival and pro-tumourigenic effects of neutrophils in human hepatocellular carcinoma","volume":"62","author":"XF Li","year":"2015","journal-title":"J Hepatol"},{"issue":"1","key":"pone.0316912.ref063","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/imr.13158","article-title":"Established and emerging roles for mitochondria in neutrophils","volume":"314","author":"S Peng","year":"2023","journal-title":"Immunol Rev"},{"issue":"2","key":"pone.0316912.ref064","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s12026-015-8655-z","article-title":"Mcl-1 is vital for neutrophil survival","volume":"62","author":"MP Murphy","year":"2015","journal-title":"Immunol Res"},{"issue":"10","key":"pone.0316912.ref065","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1007\/s10495-012-0738-x","article-title":"Differential effects of the autophagy inhibitors 3-methyladenine and chloroquine on spontaneous and TNF-alpha-induced neutrophil apoptosis","volume":"17","author":"BK Pliyev","year":"2012","journal-title":"Apoptosis"},{"issue":"4","key":"pone.0316912.ref066","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.4049\/jimmunol.170.4.1964","article-title":"The mitochondrial network of human neutrophils: role in chemotaxis, phagocytosis, respiratory burst activation, and commitment to apoptosis","volume":"170","author":"G Fossati","year":"2003","journal-title":"J Immunol"},{"issue":"11","key":"pone.0316912.ref067","doi-asserted-by":"crossref","first-page":"e79352","DOI":"10.1371\/journal.pone.0079352","article-title":"Roscovitine-induced apoptosis in neutrophils and neutrophil progenitors is regulated by the Bcl-2-family members Bim, Puma, Noxa and Mcl-1","volume":"8","author":"S Gautam","year":"2013","journal-title":"PLoS One"},{"issue":"12","key":"pone.0316912.ref068","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1182\/blood-2008-05-159145","article-title":"Selective roles for antiapoptotic MCL-1 during granulocyte development and macrophage effector function","volume":"113","author":"DA Steimer","year":"2009","journal-title":"Blood"},{"issue":"9","key":"pone.0316912.ref069","doi-asserted-by":"crossref","DOI":"10.1063\/5.0137239","article-title":"MCL-1 promiscuity and the structural resilience of its binding partners","volume":"158","author":"PJ Heckmeier","year":"2023","journal-title":"J Chem Phys"},{"issue":"7","key":"pone.0316912.ref070","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1083\/jcb.201503066","article-title":"mTOR and differential activation of mitochondria orchestrate neutrophil chemotaxis","volume":"210","author":"Y Bao","year":"2015","journal-title":"J Cell Biol"},{"key":"pone.0316912.ref071","doi-asserted-by":"crossref","first-page":"104739","DOI":"10.1016\/j.cellimm.2023.104739","article-title":"Functional responsiveness of in vitro-aged human neutrophils","volume":"390","author":"J Morin-Genest","year":"2023","journal-title":"Cell Immunol"},{"key":"pone.0316912.ref072","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.coi.2019.05.006","article-title":"The phagocyte NOX2 NADPH oxidase in microbial killing and cell signaling","volume":"60","author":"WM Nauseef","year":"2019","journal-title":"Curr Opin Immunol"},{"issue":"604","key":"pone.0316912.ref073","doi-asserted-by":"crossref","first-page":"eabb1069","DOI":"10.1126\/scitranslmed.abb1069","article-title":"Targeting multiple cell death pathways extends the shelf life and preserves the function of human and mouse neutrophils for transfusion","volume":"13","author":"Y Fan","year":"2021","journal-title":"Sci Transl Med"},{"issue":"3","key":"pone.0316912.ref074","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1093\/jleuko\/qiad078","article-title":"Closing the gap between murine neutrophils and neutrophil-like cell lines","volume":"114","author":"L-AH Allen","year":"2023","journal-title":"J Leukoc Biol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0316912","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T18:28:02Z","timestamp":1736274482000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0316912"}},"subtitle":[],"editor":[{"given":"Saeid","family":"Ghavami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,1,7]]},"references-count":74,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0316912","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,7]]}}}