{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:36:39Z","timestamp":1785411399716,"version":"3.56.0"},"reference-count":22,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K09234"],"award-info":[{"award-number":["20K09234"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K08932"],"award-info":[{"award-number":["21K08932"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K08939"],"award-info":[{"award-number":["21K08939"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"award":["20K09234"],"award-info":[{"award-number":["20K09234"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]},{"award":["21K08932"],"award-info":[{"award-number":["21K08932"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]},{"award":["21K08939"],"award-info":[{"award-number":["21K08939"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The recent rise in whole blood usage for traumatic hemorrhagic shock has renewed interest in the impact of leukocytes on hemostatic function during cold storage. This study investigated whether tissue factor (TF)-bearing extracellular vesicles (EVs) are released from human monocytic cells during cold storage or upon rewarming and whether this process is mechanistically linked to apoptosis. We further examined the contribution of superoxide anion generated by NADPH oxidase (NOX). Methods: THP-1 cells were incubated at 4 \u00b0C for up to 24 h with\/without test reagents and subsequently rewarmed at 37 \u00b0C. Cells were washed by centrifugation before rewarming as required. TF activity in the cell supernatant was quantified, EVs were analyzed by flow cytometry with size-defined gating, and NOX activity normalized to p22phox was measured by cytochrome c reduction. Results: TF levels and apoptotic cells increased during cold storage. TF release was enhanced 1\u20132 h after cell lavage following cold exposure, indicating active shedding of TF-bearing EVs rather than passive leakage from damaged membranes. Flow cytometry demonstrated that TF-bearing EVs were distinct from apoptotic vesicles, with a substantial proportion falling within the microvesicle size range. Cold exposure enhanced NOX activity. Both superoxide dismutase (SOD) and catalase inhibited TF release during cold storage; however, only SOD suppressed TF release after cell lavage. Conclusions: TF-bearing EVs are actively shed from human monocytic cells during and after cold storage via a NOX-dependent, superoxide-mediated mechanism. Extracellular SOD suppressed this procoagulant EV release, suggesting a potential strategy to modulate hemostatic alterations associated with cold-stored blood.<\/jats:p>","DOI":"10.3390\/life16050820","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:33:54Z","timestamp":1779687234000},"page":"820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ice-Cold Temperature Enhances NADPH Oxidase-Dependent Release of Tissue Factor-Bearing Extracellular Vesicles from Human Monocytic Cells"],"prefix":"10.3390","volume":"16","author":[{"given":"Akira","family":"Nishioka","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Kohnodai Hospital, National Center for the Global Health and Medicine, Ichikawa 272-8516, Japan"},{"name":"Anesthesiology and Perioperative Medicine, The Jikei University Graduate School of Medicine, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9183-0840","authenticated-orcid":false,"given":"Toshiharu","family":"Azma","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Kohnodai Hospital, National Center for the Global Health and Medicine, Ichikawa 272-8516, Japan"},{"name":"Department of Anesthesiology, Saitama Medical University Hospital, Iruma 350-0495, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Mieda","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Saitama Medical University Hospital, Iruma 350-0495, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Mio","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Jikei University School of Medicine, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mizobata, Y. 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Cancer"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/5\/820\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:51:06Z","timestamp":1779688266000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/5\/820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,15]]},"references-count":22,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["life16050820"],"URL":"https:\/\/doi.org\/10.3390\/life16050820","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,15]]}}}