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Monocytes produce P-SEP by phagocytosing neutrophil extracellular traps (NETs). Herein, we investigated whether M1 macrophages (M1 M\u03a6s) are the primary producers of P-SEP after NET phagocytosis. We co-cultured M1 M\u03a6s and NETs from healthy participants, measured P-SEP levels in the culture medium supernatant, and detected P-SEP using western blotting. When NETs were co-cultured with M1 M\u03a6s, the P-SEP level of the culture supernatant was high. Notably, we demonstrated, for the first time, the intracellular kinetics of P-SEP production by M1 M\u03a6s via NET phagocytosis: M1 M\u03a6s produced P-SEP intracellularly 15\u00a0min after NET phagocytosis and then released it extracellularly. In a sepsis mouse model, the blood NET ratio and P-SEP levels, detected using ELISA, were significantly increased (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Intracellular P-SEP analysis via flow cytometry demonstrated that lung, liver, and kidney M\u03a6s produced large amounts of P-SEP. Therefore, we identified these organs as the origin of M1 M\u03a6s that produce P-SEP during sepsis. Our data indicate that the P-SEP level reflects the trend of NETs, suggesting that monitoring P-SEP can be used to both assess NET-induced organ damage in the lungs, liver, and kidneys during sepsis and determine treatment efficacy.<\/jats:p>","DOI":"10.1038\/s41598-024-66916-y","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T12:02:10Z","timestamp":1721131330000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of organs of origin of macrophages that produce presepsin via neutrophil extracellular trap phagocytosis"],"prefix":"10.1038","volume":"14","author":[{"given":"Akihiro","family":"Kondo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuya","family":"Morinishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akishige","family":"Ikegame","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"66916_CR1","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","volume":"47","author":"L Evans","year":"2021","unstructured":"Evans, L. et al. 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