{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:44:24Z","timestamp":1782362664270,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Blood Services Intramural Grant program","award":["2015IG-JA"],"award-info":[{"award-number":["2015IG-JA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vox Sanguinis"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec><jats:title>Background and Objectives<\/jats:title><jats:p>Red\u2010blood\u2010cell (RBC) transfusion is associated with lung injury, which is further exacerbated by mechanical ventilation. Manufacturing methods of blood products differ globally and may play a role in the induction of pulmonary cell activation through alteration of the immunomodulatory property of the products. Here, the effect of different manufacturing methods on pulmonary cell activation was investigated in an <jats:italic>in vitro<\/jats:italic> model of mechanical ventilation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Pulmonary type II cells were incubated with supernatant from fresh and old RBC products obtained via whole blood filtration (WBF), red cell filtration (RCF), apheresis\u2010derived (AD) or whole blood\u2010derived (WBD) methods. Lung cells were subjected to 25% stretch for 24\u00a0h. Controls were non\u2010stretched or non\u2010incubated cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fresh but not old AD products and WBF products induce lung cell production of pro\u2010inflammatory cytokines and chemokines, which was not observed with WBD or RCF products. Effects were associated with an increased amount of platelet\u2010derived vesicles and an increased thrombin\u2010generating capacity. Mechanical stretching of lung cells induced more severe cell injury compared to un\u2010stretched controls, including alterations in the cytoskeleton, which was further augmented by incubation with AD products. In all read\u2010out parameters, RCF products seemed to induce less injury compared to the other products.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings show that manufacturing methods of RBC products impact pulmonary cell activation, which may be mediated by the generation of vesicles in the product. We suggest RBC manufacturing method may be an important factor in understanding the association between RBC transfusion and lung injury.<\/jats:p><\/jats:sec>","DOI":"10.1111\/vox.12911","type":"journal-article","created":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T04:34:25Z","timestamp":1584074065000},"page":"395-404","source":"Crossref","is-referenced-by-count":4,"title":["Red\u2010blood\u2010cell manufacturing methods and storage solutions differentially induce pulmonary cell activation"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1923-083X","authenticated-orcid":false,"given":"Mathijs R.","family":"Wirtz","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Intensive Care and Anesthesiology Amsterdam UMC University of Amsterdam Amsterdam the Netherlands"},{"name":"Department of Intensive Care Medicine Amsterdam UMC University of Amsterdam Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruqayyah J.","family":"Almizraq","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Pathology University of Alberta Edmonton AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina C.","family":"Weber","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Intensive Care and Anesthesiology Amsterdam UMC University of Amsterdam Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Norris","sequence":"additional","affiliation":[{"name":"Blood Systems Research Institute San Francisco CA USA"},{"name":"Departments of Laboratory Medicine and Medicine University of California San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchitra","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine University of California San Francisco CA USA"},{"name":"Blood Centers of the Pacific (member of Blood Systems) San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip C.","family":"Spinella","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Critical Care Washington University in St Louis St Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Muszynski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Critical Care Medicine Nationwide Children's Hospital Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"P. 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