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However, little distinction has been made between these two forms of circulating extracellular histones. Our study detected increased circulating nucleosomes in acute lung injury patients. Further, our group identified nucleosomes as the leading form of extracellular histones compared to free histones in the plasma of COVID\u201019 patients, underscoring the necessity to reassess the forms of circulating histones and nucleosome contributions to immunopathology. Functionally, nucleosomes activated macrophages and induced inflammation in different organs. Mechanistically, we observed nucleosomes activating the NF\u2010\u03baB signaling, while inhibition of NF\u2010\u03baB by sulfasalazine attenuated nucleosome\u2010induced macrophage activation. Taken together, our study indicates that extracellular histones are predominantly released as nucleosomes, playing a critical role in the inflammation of the lungs and other organs.<\/jats:p>","DOI":"10.1096\/fj.202401571rr","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T11:18:56Z","timestamp":1732879136000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The impact of circulating nucleosomes on inflammation in acute lung injury"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4377-5706","authenticated-orcid":false,"given":"Saugata","family":"Dutta","sequence":"first","affiliation":[{"name":"Clinical and Experimental Therapeutics, College of Pharmacy University of Georgia and Charlie Norwood VA Medical Center  Augusta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1683-4205","authenticated-orcid":false,"given":"Yin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Therapeutics, College of Pharmacy University of Georgia and Charlie Norwood VA Medical Center  Augusta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4353-6043","authenticated-orcid":false,"given":"Sultan","family":"Almuntashiri","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Therapeutics, College of Pharmacy University of Georgia and Charlie Norwood VA Medical Center  Augusta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3017-0230","authenticated-orcid":false,"given":"Payaningal R.","family":"Somanath","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Therapeutics, College of Pharmacy University of Georgia and Charlie Norwood VA Medical Center  Augusta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4814-6757","authenticated-orcid":false,"given":"Shaheen","family":"Islam","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care &amp; 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