{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:07:19Z","timestamp":1781104039286,"version":"3.54.1"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neutrophils are key players in innate immunity, forming neutrophil extracellular traps (NETs) to defend against infections. However, excess NET formation is implicated in inflammatory conditions such as sepsis and immunothrombosis. Studying NET formation in isolated neutrophils provides important mechanistic insights but does not reflect the complexity of immune interactions in whole blood, limiting our understanding of neutrophil responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study investigates chromatin accessibility changes using Assay for Transposase-Accessible Chromatin with sequencing (ATAC-Seq) during phorbol 12-myristate 13-acetate (PMA) induced NET formation in whole blood. We compared chromatin accessibility patterns in neutrophils following PMA treatment in isolation and whole blood to assess the impact of other immune cells and signaling environment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Whole blood PMA stimulation elicited consistent chromatin accessibility changes across donors, demonstrating organized chromatin decondensation during NET formation. The chromatin response was characterized by increased accessibility in genomic regions enriched for immune-specific pathways, highlighting the role of immune cell interactions in NET formation. Differentially accessible regions (DARs) present following PMA induction in whole blood and isolated neutrophils showed greater association with NET-related and inflammatory transcription factors, while DARs specific to isolated neutrophils showed fewer relevant motifs. Pathway analysis indicated that whole blood responses involved more robust activation of immune-specific pathways, such as interleukin and cytokine signaling, compared to isolated neutrophils.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings underscore the importance of studying NET formation within a whole blood environment to capture the complexity of neutrophil responses and immune cell interactions. This understanding is crucial for identifying effective therapeutic targets in NET-associated inflammatory diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1515430","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T05:07:16Z","timestamp":1741064836000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Chromatin changes associated with neutrophil extracellular trap formation in whole blood reflect complex immune signaling"],"prefix":"10.3389","volume":"16","author":[{"given":"Justin","family":"Cayford","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandi","family":"Atteberry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akanksha","family":"Singh-Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Retter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin P.","family":"Berman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa K.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1093\/rb\/rbw041","article-title":"An overview of the role of neutrophils in innate immunity, inflammation and host-biomaterial integration","volume":"4","author":"Selders","year":"2017","journal-title":"Regener Biomater."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.105","article-title":"Neutrophil extracellular traps in immunity and disease","volume":"18","author":"Papayannopoulos","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B3","doi-asserted-by":"publisher","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":"B4","doi-asserted-by":"publisher","first-page":"113","DOI":"10.3389\/fphys.2018.00113","article-title":"Neutrophil: A cell with many roles in inflammation or several cell types","volume":"9","author":"Rosales","year":"2018","journal-title":"Front Physiol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.5114\/ceji.2014.42136","article-title":"Neutrophil extracellular traps in physiology and pathology","volume":"39","author":"Manda","year":"2014","journal-title":"Cent Eur J Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1159\/000489829","article-title":"Neutrophil extracellular traps in the second decade","volume":"10","author":"Brinkmann","year":"2018","journal-title":"J Innate Immun"},{"key":"B7","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1172\/JCI82224","article-title":"Sepsis-induced immune dysfunction: can immune therapies reduce mortality","volume":"126","author":"Delano","year":"2016","journal-title":"J Clin Invest"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-021-00552-1","article-title":"Interplay between inflammation and thrombosis in cardiovascular pathology","volume":"18","author":"Stark","year":"2021","journal-title":"Nat Rev Cardiol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"291","DOI":"10.3389\/fvets.2018.00291","article-title":"A comparative review of neutrophil extracellular traps in sepsis","volume":"5","author":"Li","year":"2018","journal-title":". 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