{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:43:08Z","timestamp":1791423788316,"version":"4.3.3"},"reference-count":83,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,9,6]],"date-time":"2017-09-06T00:00:00Z","timestamp":1504656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Although transfusion is a lifesaving intervention, it may be associated with significant morbidity in injured patients. We hypothesize that stored red blood cells (RBCs) induce proinflammatory activation of human pulmonary microvascular endothelial cells (HMVECs) resulting in neutrophil (PMN) adhesion and predisposition to acute lung injury (ALI).<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY DESIGN AND METHODS<\/jats:title><jats:p>Ten units of RBCs were collected; 50% (by weight) were leukoreduced (LR\u2010RBCs) and the remainder was unmodified and stored in additive solution\u20105 (AS\u20105). An additional 10 units of RBCs were collected, leukoreduced, and stored in AS\u20103. HMVECs were incubated with [10%\u201040%]<jats:sub>FINAL<\/jats:sub> of the supernatants on Day (D)1 to D42 of storage, lipid extracts, and purified lipids. Endothelial surface expression of intercellular adhesion molecule\u20101 (ICAM\u20101), interleukin (IL)\u20108 release, and PMN adhesion to HMVECs were measured. HMVEC signaling via the BLT2 receptor was evaluated. Supernatants and lipids were also employed as the first event in a two\u2010event model of ALI.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The supernatants [10%\u201040%]<jats:sub>FINAL<\/jats:sub> from D21 LR\u2010RBCs and D42 RBCs and LR\u2010RBCs and the lipids from D42 stored in AS\u20105 induced increased ICAM\u20101 surface expression on endothelium, IL\u20108 release, and PMN adhesion. In addition, the supernatants [20%\u201040%]<jats:sub>FINAL<\/jats:sub> from D21 and D42 RBCs in AS\u20105 also increased endothelial surface expression of ICAM\u20101. D42 supernatants and lipids also caused coprecipitation of \u03b2\u2010arrestin\u20101 with BLT2, protein kinase C (PKC)\u03b2<jats:sub>I<\/jats:sub>, and PKC\u03b4 and served as the first event in a two\u2010event rodent model of ALI.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Lipids that accumulate during RBC storage activate endothelium and predispose to ALI, which may explain some of the adverse events associated with the transfusion of critically injured patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.14271","type":"journal-article","created":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T13:17:11Z","timestamp":1504790231000},"page":"2690-2700","source":"Crossref","is-referenced-by-count":12,"title":["Supernatants and lipids from stored red blood cells activate pulmonary microvascular endothelium through the BLT2 receptor and protein kinase C activation"],"prefix":"10.1111","volume":"57","author":[{"given":"Christopher C.","family":"Silliman","sequence":"first","affiliation":[{"name":"Research Laboratory Bonfils Blood Center Denver Colorado"},{"name":"Department of Surgery School of Medicine, University of Colorado at Denver Aurora Colorado"},{"name":"Department of Pediatrics School of Medicine, University of Colorado at Denver Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marguerite R.","family":"Kelher","sequence":"additional","affiliation":[{"name":"Research Laboratory Bonfils Blood Center Denver Colorado"},{"name":"Department of Surgery School of Medicine, University of Colorado at Denver Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samina Y.","family":"Khan","sequence":"additional","affiliation":[{"name":"Research Laboratory Bonfils Blood Center Denver Colorado"},{"name":"Department of Pediatrics School of Medicine, University of Colorado at Denver Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Bernadette","family":"West","sequence":"additional","affiliation":[{"name":"Research Laboratory Bonfils Blood Center Denver Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan J.D.","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"Research Laboratory Bonfils Blood Center Denver Colorado"},{"name":"Department of Pediatrics School of Medicine, University of Colorado at Denver Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Elzi","sequence":"additional","affiliation":[{"name":"Research Laboratory Bonfils Blood Center Denver Colorado"},{"name":"Department of Surgery School of Medicine, University of Colorado at Denver Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"England","sequence":"additional","affiliation":[{"name":"Research Laboratory Bonfils Blood Center Denver Colorado"},{"name":"Department of Surgery School of Medicine, University of Colorado at Denver Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Bjornsen","sequence":"additional","affiliation":[{"name":"Research Laboratory Bonfils Blood Center Denver Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan A.","family":"Kuldanek","sequence":"additional","affiliation":[{"name":"Research Laboratory Bonfils Blood Center Denver Colorado"},{"name":"Department of Pediatrics School of Medicine, University of Colorado at Denver Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anirban","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Surgery School of Medicine, University of Colorado at Denver Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.8.8.8181668"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.55.5.662"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.07.030"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-09-177857"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00540.2001"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e318256de38"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2014.05.015"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1994.01420250051006"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005373-199808000-00014"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e3181fa0019"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9610(99)00239-1"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e318170a9ce"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa070403"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e31817c9687"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0000000000000583"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2011.03186.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2012.03564.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.1996.36296181925.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1841"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e3181faceb3"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.11.7039"},{"key":"e_1_2_8_23_1","first-page":"684","article-title":"Partial characterization of lipids that develop during the routine storage of blood and prime the neutrophil NADPH oxidase","volume":"124","author":"Silliman CC","year":"1994","journal-title":"J Lab Clin Med"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3A0813-420RRR"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00259.2011"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.111.6.3129"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2011.03.018"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2010.07.016"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4942"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0445OC"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.16.12.1909"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.185793"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(80)90189-0"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199305203282005"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1086\/649557"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1423-0410.2009.01289.x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-10-532424"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01451"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1109237"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.12.8192"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.06.023"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901735"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.481283"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.267054"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.301206"},{"key":"e_1_2_8_46_1","doi-asserted-by":"crossref","unstructured":"MackJP KahnSR TinmouthA et al. Abstract 96. Dose\u2010dependent effect of stored red blood: results of a sub\u2010group analysis of the Age of Blood Evaluation (ABLE) Trial. Blood Meeting Abstracts2016;128[22].","DOI":"10.1182\/blood.V128.22.96.96"},{"key":"e_1_2_8_47_1","first-page":"24","article-title":"Risk factors for trauma\u2010induced coagulopathy\u2010 and transfusion\u2010associated multiple organ failure in severely injured trauma patients","volume":"2","author":"Balvers K","year":"2015","journal-title":"Front Med (Lausanne)"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3181948a97"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.140.5.432"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e3181e76274"},{"key":"e_1_2_8_51_1","first-page":"290","article-title":"The age of red blood cells is associated with bacterial infections in critically ill trauma patients","volume":"10","author":"Juffermans NP","year":"2012","journal-title":"Blood Transfus"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2009.02211.x"},{"key":"e_1_2_8_53_1","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1177\/000313480407000418","article-title":"Age, blood transfusion, and survival after trauma","volume":"70","author":"Mostafa G","year":"2004","journal-title":"Am Surg"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1177\/000313480507100918"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.137.6.711"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc8050"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2011.03466.x"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2011.03098.x"},{"key":"e_1_2_8_59_1","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1177\/000313481307900824","article-title":"When enough is enough: impact of packed red blood cells in massive transfusion outcomes","volume":"79","author":"Long K","year":"2013","journal-title":"Am Surg"},{"key":"e_1_2_8_60_1","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1177\/000313480907500408","article-title":"Transfusion, not just injury severity, leads to posttrauma infection: a matched cohort study","volume":"75","author":"Sadjadi J","year":"2009","journal-title":"Am Surg"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0000000000000147"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc2405"},{"key":"e_1_2_8_63_1","first-page":"194","article-title":"Neutrophil priming and activation in the pathogenesis of postinjury multiple organ failure","volume":"4","author":"Partrick DA","year":"1996","journal-title":"New Horiz"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114545"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-6576.2010.02266.x"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjsurg.2010.02.003"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e318294672d"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840020516"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1040630"},{"key":"e_1_2_8_70_1","first-page":"21","article-title":"Liver transplantation: current concepts","volume":"139","author":"Wall WJ.","year":"1988","journal-title":"CMAJ"},{"key":"e_1_2_8_71_1","first-page":"131","article-title":"The accumulation of lipids and proteins during red blood cell storage: the roles of leucoreduction and experimental filtration","volume":"15","author":"Silliman CC","year":"2017","journal-title":"Blood Transfus"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1111\/vox.12042"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3412"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000394"},{"key":"e_1_2_8_75_1","first-page":"s7","article-title":"Time to revisit red blood cell additive solutions and storage conditions: a role for \u201comics\u201d analyses","volume":"10","author":"Sparrow RL.","year":"2012","journal-title":"Blood Transfus"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1111\/vox.12193"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.12975"},{"key":"e_1_2_8_78_1","first-page":"s46","article-title":"Red blood cell storage in SAGM and AS3: a comparison through the membrane two\u2010dimensional electrophoresis proteome","volume":"10","author":"D'Amici GM","year":"2012","journal-title":"Blood Transfus"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2012.03.012"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmrv.2014.01.003"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.051789"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000001614"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1111\/vox.12453"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0446OC"}],"container-title":["Transfusion"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ftrf.14271","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.14271","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T17:44:20Z","timestamp":1695491060000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/trf.14271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,6]]},"references-count":83,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1111\/trf.14271"],"URL":"https:\/\/doi.org\/10.1111\/trf.14271","archive":["Portico"],"relation":{},"ISSN":["0041-1132","1537-2995"],"issn-type":[{"value":"0041-1132","type":"print"},{"value":"1537-2995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,6]]}}}