{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:00:17Z","timestamp":1792789217389,"version":"4.5.0"},"reference-count":73,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R00GM147910"],"award-info":[{"award-number":["R00GM147910"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Acute respiratory distress syndrome (ARDS) is an inflammatory pulmonary condition that remains at alarming rates of fatality, with neutrophils playing a vital role in its pathogenesis. Beyond their classical antimicrobial functions, neutrophils contribute to pulmonary injury via the release of reactive oxygen species, proteolytic enzymes, and neutrophil extracellular traps (NETs). To identify targets for treatment, it was found that epigenetic mechanisms, including histone modifications, hypomethylation, hypermethylation, and non-coding RNAs, regulate neutrophil phenotypic plasticity, survival, and inflammatory potential. It has been identified that neutrophils in ARDS patients exhibit abnormal methylation patterns and are associated with altered gene expression and prolonged neutrophil activation, thereby contributing to sustained inflammation. Histone citrullination, particularly via PAD4, facilitates NETosis, while histone acetylation status modulates chromatin accessibility and inflammatory gene expression. MicroRNAs have also been shown to regulate neutrophil activity, with miR-223 and miR-146a potentially being biomarkers and therapeutic targets. Neutrophil heterogeneity, as evidenced by distinct subsets such as low-density neutrophils (LDNs), varies across ARDS etiologies, including COVID-19. Single-cell RNA sequencing analyses, including the use of trajectory analysis, have revealed transcriptionally distinct neutrophil clusters with differential activation states. These studies support the use of epigenetic inhibitors, including PAD4, HDAC, and DNMT modulators, in therapeutic intervention. While the field has been enlightened with new findings, challenges in translational application remain an issue due to species differences, lack of stratification tools, and heterogeneity in ARDS presentation. This review describes how targeting neutrophil epigenetic regulators could help regulate hyperinflammation, making epigenetic modulation a promising area for precision therapeutics in ARDS.<\/jats:p>","DOI":"10.3390\/cells14151151","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T12:56:43Z","timestamp":1753448203000},"page":"1151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Epigenetic Regulation of Neutrophils in ARDS"],"prefix":"10.3390","volume":"14","author":[{"given":"Jordan E.","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology & Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2229-2090","authenticated-orcid":false,"given":"Zannatul","family":"Mauya","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology & Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Walkup","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology & Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaquria","family":"Adderley","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Cell Biology & Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8550-3739","authenticated-orcid":false,"given":"Kiesha","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology & Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ramji, H.F., Hafiz, M., Altaq, H.H., Hussain, S.T., and Chaudry, F. (2023). Acute Respiratory Distress Syndrome; A Review of Recent Updates and a Glance into the Future. Diagnostics, 13.","DOI":"10.3390\/diagnostics13091528"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Yang, P., Wu, T., Yu, M., Chen, F., Wang, C., Yuan, J., Xu, J., and Zhang, G. (2020). A new method for identifying the acute respiratory distress syndrome disease based on noninvasive physiological parameters. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0226962"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ccc.2023.12.003","article-title":"Acute Respiratory Distress Syndrome: Definition, Diagnosis, and Routine Management","volume":"40","author":"Yang","year":"2024","journal-title":"Crit. Care Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e2250010","DOI":"10.1002\/eji.202250010","article-title":"Neutrophil activation and neutrophil extracellular traps (NETs) in COVID-19 ARDS and immunothrombosis","volume":"53","author":"Cesta","year":"2023","journal-title":"Eur. J. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41423-020-0412-0","article-title":"Neutrophil chemoattractant receptors in health and disease: Double-edged swords","volume":"17","author":"Metzemaekers","year":"2020","journal-title":"Cell Mol. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1136\/thoraxjnl-2016-208597","article-title":"Evidence for chemokine synergy during neutrophil migration in ARDS","volume":"72","author":"Williams","year":"2017","journal-title":"Thorax"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ohms, M., M\u00f6ller, S., and Laskay, T. (2020). An Attempt to Polarize Human Neutrophils Toward N1 and N2 Phenotypes in vitro. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00532"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41572-019-0069-0","article-title":"Acute respiratory distress syndrome","volume":"5","author":"Matthay","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Calle-Fabregat, C., Morante-Palacios, O., and Ballestar, E. (2020). Understanding the Relevance of DNA Methylation Changes in Immune Differentiation and Disease. Genes, 11.","DOI":"10.3390\/genes11010110"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hamam, H.J., Khan, M.A., and Palaniyar, N. (2019). Histone Acetylation Promotes Neutrophil Extracellular Trap Formation. Biomolecules, 9.","DOI":"10.3390\/biom9010032"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1111\/cei.12359","article-title":"Acetylated histones contribute to the immunostimulatory potential of neutrophil extracellular traps in systemic lupus erythematosus","volume":"179","author":"Pieterse","year":"2015","journal-title":"Clin. Exp. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.cell.2012.12.018","article-title":"Latent enhancers activated by stimulation in differentiated cells","volume":"152","author":"Ostuni","year":"2013","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nrg.2016.59","article-title":"The molecular hallmarks of epigenetic control","volume":"17","author":"Allis","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.2217\/epi.15.39","article-title":"Methyl-CpG-binding domain proteins: Readers of the epigenome","volume":"7","author":"Du","year":"2015","journal-title":"Epigenomics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1016\/j.bbamcr.2008.07.015","article-title":"The cell biology of DNA methylation in mammals","volume":"1783","author":"Prokhortchouk","year":"2008","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/hdy.2010.54","article-title":"Epigenetics and gene expression","volume":"105","author":"Gibney","year":"2010","journal-title":"Heredity"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA Methylation and Its Basic Function","volume":"38","author":"Moore","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Castillo-Aguilera, O., Depreux, P., Halby, L., Arimondo, P.B., and Goossens, L. (2017). DNA Methylation Targeting: The DNMT\/HMT Crosstalk Challenge. Biomolecules, 7.","DOI":"10.3390\/biom7010003"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nrg3230","article-title":"Functions of DNA methylation: Islands, start sites, gene bodies and beyond","volume":"13","author":"Jones","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/978-94-007-4525-4_13","article-title":"The role of DNA methylation and histone modifications in transcriptional regulation in humans","volume":"61","author":"Miller","year":"2013","journal-title":"Subcell. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/cr.2011.22","article-title":"Regulation of chromatin by histone modifications","volume":"21","author":"Bannister","year":"2011","journal-title":"Cell Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.molcel.2008.02.014","article-title":"Histone Ubiquitination: Triggering Gene Activity","volume":"29","author":"Weake","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kraus, R.F., and Gruber, M.A. (2021). Neutrophils-From Bone Marrow to First-Line Defense of the Innate Immune System. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.767175"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev-pathol-020712-164023","article-title":"The multifaceted functions of neutrophils","volume":"9","author":"Mayadas","year":"2014","journal-title":"Annu. Rev. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1001\/jama.2016.0291","article-title":"Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries","volume":"315","author":"Bellani","year":"2016","journal-title":"JAMA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.it.2007.06.002","article-title":"Neutrophil granules: A library of innate immunity proteins","volume":"28","author":"Borregaard","year":"2007","journal-title":"Trends Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/JLB.4MIR0220-574RR","article-title":"Neutrophils at the crossroads of innate and adaptive immunity","volume":"108","author":"Rosales","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e171659","DOI":"10.1172\/jci.insight.171659","article-title":"Emergence of dysfunctional neutrophils with a defect in arginase-1 release in severe COVID-19","volume":"9","author":"Dwivedi","year":"2024","journal-title":"JCI Insight"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1172\/JCI41649","article-title":"CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow","volume":"120","author":"Eash","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/mi.2016.80","article-title":"IL-17A-mediated neutrophil recruitment limits expansion of segmented filamentous bacteria","volume":"10","author":"Flannigan","year":"2017","journal-title":"Mucosal Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s10020-025-01187-5","article-title":"Interaction of low-density neutrophils with other immune cells in the mechanism of inflammation","volume":"31","author":"Fu","year":"2025","journal-title":"Mol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3166","DOI":"10.1182\/blood.2021013565","article-title":"Formation of neutrophil extracellular traps requires actin cytoskeleton rearrangements","volume":"139","author":"Sprenkeler","year":"2022","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"462","DOI":"10.4049\/jimmunol.2200863","article-title":"Sfxn5 Regulation of Actin Polymerization for Neutrophil Spreading Depends on a Citrate-Cholesterol-PI(4,5)P2 Pathway","volume":"211","author":"Zhang","year":"2023","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"117598","DOI":"10.1016\/j.ecoenv.2024.117598","article-title":"Lead-induced actin polymerization aggravates neutrophil extracellular trap formation and contributes to vascular inflammation","volume":"290","author":"Nong","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2119\/molmed.2010.00138","article-title":"Contribution of Neutrophils to Acute Lung Injury","volume":"17","author":"Grommes","year":"2011","journal-title":"Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.jointm.2024.02.002","article-title":"Glucocorticoid therapy for acute respiratory distress syndrome: Current concepts","volume":"4","author":"Zhao","year":"2024","journal-title":"J. Intensive Med."},{"key":"ref_37","first-page":"1581038","article-title":"The Neutrophil-to-Lymphocyte Ratio is Associated with the Requirement and the Duration of Invasive Mechanical Ventilation in Acute Respiratory Distress Syndrome Patients: A Retrospective Study","volume":"2022","author":"Yang","year":"2022","journal-title":"Can. Respir. J."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Belchamber, K.B.R., Thein, O.S., Hazeldine, J., Grudzinska, F.S., Faniyi, A.A., Hughes, M.J., Jasper, A.E., Yip, K.P., Crowley, L.E., and Lugg, S.T. (2022). Dysregulated Neutrophil Phenotype and Function in Hospitalised Non-ICU COVID-19 Pneumonia. Cells, 11.","DOI":"10.3390\/cells11182901"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Cheng, O.Z., and Palaniyar, N. (2013). NET balancing: A problem in inflammatory lung diseases. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00001"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1702590","DOI":"10.1183\/13993003.02590-2017","article-title":"Impaired efferocytosis and neutrophil extracellular trap clearance by macrophages in ARDS","volume":"52","author":"Uhel","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1186\/s12967-022-03737-5","article-title":"DNA methylation predicts the outcome of COVID-19 patients with acute respiratory distress syndrome","volume":"20","author":"Bradic","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"243","DOI":"10.2147\/IJGM.S287960","article-title":"Identification of Genes with Altered Methylation and Its Role in Early Diagnosis of Sepsis-Induced Acute Respiratory Distress Syndrome","volume":"14","author":"Feng","year":"2021","journal-title":"Int. J. Gen. Med."},{"key":"ref_43","first-page":"A61","article-title":"S97 Neutrophil Epigenetic Signatures in the Context of Acute Respiratory Distress Syndrome","volume":"77","author":"Xu","year":"2022","journal-title":"Thorax"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s12931-024-02676-7","article-title":"Role and intervention of PAD4 in NETs in acute respiratory distress syndrome","volume":"25","author":"Liu","year":"2024","journal-title":"Respir. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"103256","DOI":"10.1016\/j.isci.2021.103256","article-title":"Zinc-dependent histone deacetylases drive neutrophil extracellular trap formation and potentiate local and systemic inflammation","volume":"24","author":"Poli","year":"2021","journal-title":"iScience"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13075-025-03487-x","article-title":"MiR-223 within neutrophil axis promotes Th17 expansion by PI3K-AKT pathway in systemic lupus erythematosus","volume":"27","author":"Zhang","year":"2025","journal-title":"Arthritis Res. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s12931-020-01374-4","article-title":"MiR-223 plays a protecting role in neutrophilic asthmatic mice through the inhibition of NLRP3 inflammasome","volume":"21","author":"Xu","year":"2020","journal-title":"Respir. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e15494","DOI":"10.14814\/phy2.15494","article-title":"Identification of circulating microvesicle-encapsulated miR-223 as a potential novel biomarker for ARDS","volume":"10","author":"Almuntashiri","year":"2022","journal-title":"Physiol. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.3324\/haematol.2019.240226","article-title":"miR-146a is a pivotal regulator of neutrophil extracellular trap formation promoting thrombosis","volume":"106","author":"Arroyo","year":"2021","journal-title":"Haematologica"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Gysemans, C., Beya, M., Pedace, E., and Mathieu, C. (2025). Exploring Neutrophil Heterogeneity and Plasticity in Health and Disease. Biomedicines, 13.","DOI":"10.3390\/biomedicines13030597"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1002\/JLB.5HR0120-459R","article-title":"On the origin of low-density neutrophils","volume":"107","author":"Hassani","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e70063","DOI":"10.1002\/mco2.70063","article-title":"Neutrophil heterogeneity and plasticity: Unveiling the multifaceted roles in health and disease","volume":"6","author":"He","year":"2025","journal-title":"MedComm (2020)"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e152291","DOI":"10.1172\/jci.insight.152291","article-title":"A functionally distinct neutrophil landscape in severe COVID-19 reveals opportunities for adjunctive therapies","volume":"7","author":"Panda","year":"2022","journal-title":"JCI Insight"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1038\/s41418-021-00805-z","article-title":"Patients with COVID-19: In the dark-NETs of neutrophils","volume":"28","author":"Ackermann","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_55","first-page":"e138999","article-title":"Neutrophil extracellular traps in COVID-19","volume":"5","author":"Zuo","year":"2020","journal-title":"JCI Insight"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/S2213-2600(20)30366-0","article-title":"Prevalence of phenotypes of acute respiratory distress syndrome in critically ill patients with COVID-19: A prospective observational study","volume":"8","author":"Sinha","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Cabrera, L.E., Jokiranta, S.T., M\u00e4ki, S., Miettinen, S., Kant, R., Kareinen, L., Sironen, T., Pietil\u00e4, J.-P., Kantele, A., and Kek\u00e4l\u00e4inen, E. (2024). The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons. PLOS Pathog., 20.","DOI":"10.1371\/journal.ppat.1012368"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"147564","DOI":"10.1172\/jci.insight.147564","article-title":"NETosis in the pathogenesis of acute lung injury following cutaneous chemical burns","volume":"6","author":"Surolia","year":"2021","journal-title":"JCI Insight"},{"key":"ref_59","unstructured":"Bonilha, C.S., Veras, F.P., Dos Santos Ramos, A., Gomes, G.F., Rodrigues Lemes, R.M., Arruda, E., Alves-Filho, J.C., Cunha, T.M., and Cunha, F.Q. PAD4 inhibition impacts immune responses in SARS-CoV-2 infection, Mucosal Immunol., in press."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3561","DOI":"10.1158\/0008-5472.CAN-21-4045","article-title":"A Novel Selective Inhibitor JBI-589 Targets PAD4-Mediated Neutrophil Migration to Suppress Tumor Progression","volume":"82","author":"Deng","year":"2022","journal-title":"Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Gajendran, C., Fukui, S., Sadhu, N.M., Zainuddin, M., Rajagopal, S., Gosu, R., Gutch, S., Fukui, S., Sheehy, C.E., and Chu, L. (2023). Alleviation of arthritis through prevention of neutrophil extracellular traps by an orally available inhibitor of protein arginine deiminase 4. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-30246-2"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1465-9921-11-33","article-title":"Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice","volume":"11","author":"Ni","year":"2010","journal-title":"Respir. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1182\/blood-2015-01-624023","article-title":"P-selectin promotes neutrophil extracellular trap formation in mice","volume":"126","author":"Etulain","year":"2015","journal-title":"Blood"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1165\/rcmb.2013-0142OC","article-title":"Proteinase-activated receptor-1, CCL2, and CCL7 regulate acute neutrophilic lung inflammation","volume":"50","author":"Mercer","year":"2014","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1038\/s41374-019-0242-9","article-title":"Activation of death-associated protein kinase 1 promotes neutrophil apoptosis to accelerate inflammatory resolution in acute respiratory distress syndrome","volume":"99","author":"Cui","year":"2019","journal-title":"Lab. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.trecan.2016.12.006","article-title":"Mouse versus Human Neutrophils in Cancer: A Major Knowledge Gap","volume":"3","author":"Eruslanov","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Pilling, D., Consalvo, K.M., Kirolos, S.A., and Gomer, R.H. (2025). Differences between human male and female neutrophils with respect to which RNAs are present in polysomes. bioRxiv.","DOI":"10.1101\/2025.05.07.652701"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.ccm.2021.04.012","article-title":"Gender Differences in Critical Illness and Critical Care Research","volume":"42","author":"Lat","year":"2021","journal-title":"Clin. Chest Med."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Gujski, M., Jankowski, M., Rabczenko, D., Gorynski, P., and Juszczyk, G. (2022). The Prevalence of Acute Respiratory Distress Syndrome (ARDS) and Outcomes in Hospitalized Patients with COVID-19-A Study Based on Data from the Polish National Hospital Register. Viruses, 14.","DOI":"10.3390\/v14010076"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Al-Kuraishy, H.M., Al-Gareeb, A.I., Faidah, H., Al-Maiahy, T.J., Cruz-Martins, N., and Batiha, G.E. (2021). The Looming Effects of Estrogen in COVID-19: A Rocky Rollout. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.649128"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1089\/sur.2024.016","article-title":"Sex Differences of Neutrophil Extracellular Traps on Lipopolysaccharide-Stimulated Human Neutrophils","volume":"25","author":"Ishikawa","year":"2024","journal-title":"Surg. Infect."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1007\/s00134-023-07238-x","article-title":"Racial and ethnic minority participants in clinical trials of acute respiratory distress syndrome","volume":"49","author":"Papoutsi","year":"2023","journal-title":"Intensive Care Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s40246-024-00585-w","article-title":"A genome-wide association study of neutrophil count in individuals associated to an African continental ancestry group facilitates studies of malaria pathogenesis","volume":"18","author":"Constantinescu","year":"2024","journal-title":"Hum. Genom."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/15\/1151\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:16:07Z","timestamp":1760033767000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/15\/1151"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,25]]},"references-count":73,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["cells14151151"],"URL":"https:\/\/doi.org\/10.3390\/cells14151151","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,25]]}}}