{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:45:43Z","timestamp":1791312343864,"version":"4.3.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":1183,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007137","name":"Helse Nord RHF","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100007137","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Odd Fellow Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Venous air embolism, which may complicate medical and surgical procedures, activates complement and triggers thromboinflammation. In lepirudin-anticoagulated human whole blood, we examined the effect of air bubbles on complement and its role in thromboinflammation. Whole blood from 16 donors was incubated with air bubbles without or with inhibitors of C3, C5, C5aR1, or CD14. Complement activation, hemostasis, and cytokine release were measured using ELISA and quantitative PCR. Compared with no air, incubating blood with air bubbles increased, on average, C3a 6.5-fold, C3bc 6-fold, C3bBbP 3.7-fold, C5a 4.6-fold, terminal complement complex sC5b9 3.6-fold, prothrombin fragments 1+2 (PTF1+2) 25-fold, tissue factor mRNA (TF-mRNA) 26-fold, microparticle tissue factor 6.1-fold, \u03b2-thromboglobulin 26-fold (all p &amp;lt; 0.05), and 25 cytokines 11-fold (range, 1.5\u201378-fold; all p &amp;lt; 0.0001). C3 inhibition attenuated complement and reduced PTF1+2 2-fold, TF-mRNA 5.4-fold, microparticle tissue factor 2-fold, and the 25 cytokines 2.7-fold (range, 1.4\u20134.9-fold; all p &amp;lt; 0.05). C5 inhibition reduced PTF1+2 2-fold and TF-mRNA 12-fold (all p &amp;lt; 0.05). C5 or CD14 inhibition alone reduced three cytokines, including IL-1\u03b2 (p = 0.02 and p = 0.03). Combined C3 and CD14 inhibition reduced all cytokines 3.9-fold (range, 1.3\u20139.5-fold; p &amp;lt; 0.003) and was most pronounced for IL-1\u03b2 (3.2- versus 6.4-fold), IL-6 (2.5- versus 9.3-fold), IL-8 (4.9- versus 8.6-fold), and IFN-\u03b3 (5- versus 9.5-fold). Antifoam activated complement and was avoided. PTF1+2 was generated in whole blood but not in plasma. In summary, air bubbles activated complement and triggered a C3-driven thromboinflammation. C3 inhibition reduced all mediators, whereas C5 inhibition reduced only TF-mRNA. Combined C5 and CD14 inhibition reduced IL-1\u03b2 release. These data have implications for future mechanistic studies and possible pharmacological interventions in patients with air embolism.<\/jats:p>","DOI":"10.4049\/jimmunol.2100308","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T15:10:22Z","timestamp":1635952222000},"page":"2828-2840","source":"Crossref","is-referenced-by-count":23,"title":["Air Bubbles Activate Complement and Trigger Hemostasis and C3-Dependent Cytokine Release Ex Vivo in Human Whole Blood"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2685-3047","authenticated-orcid":false,"given":"Benjamin S","family":"Storm","sequence":"first","affiliation":[{"name":"Department of Anesthesia and Intensive Care Medicine, Surgical Clinic, Nordland Hospital , Bod\u00f8 ,","place":["Norway"]},{"name":"Institute of Clinical Medicine, UiT The Arctic University of Norway , Troms\u00f8 ,","place":["Norway"]},{"name":"Faculty of Nursing and Health Sciences, Nord University , Bod\u00f8 ,","place":["Norway"]},{"name":"Research Laboratory, Nordland Hospital Trust , Bod\u00f8 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7420-3762","authenticated-orcid":false,"given":"Dorte","family":"Christiansen","sequence":"additional","affiliation":[{"name":"Research Laboratory, Nordland Hospital Trust , Bod\u00f8 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilde","family":"Fure","sequence":"additional","affiliation":[{"name":"Research Laboratory, Nordland Hospital Trust , Bod\u00f8 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7175-5334","authenticated-orcid":false,"given":"Judith K","family":"Ludviksen","sequence":"additional","affiliation":[{"name":"Research Laboratory, Nordland Hospital Trust , Bod\u00f8 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1750-8065","authenticated-orcid":false,"given":"Corinna","family":"Lau","sequence":"additional","affiliation":[{"name":"Research Laboratory, Nordland Hospital Trust , Bod\u00f8 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9370-5776","authenticated-orcid":false,"given":"John D","family":"Lambris","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1382-911X","authenticated-orcid":false,"given":"Trent M","family":"Woodruff","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, The University of Queensland , St. Lucia, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole-Lars","family":"Brekke","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, UiT The Arctic University of Norway , Troms\u00f8 ,","place":["Norway"]},{"name":"Research Laboratory, Nordland Hospital Trust , Bod\u00f8 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonje","family":"Braaten","sequence":"additional","affiliation":[{"name":"Faculty of Nursing and Health Sciences, Nord University , Bod\u00f8 ,","place":["Norway"]},{"name":"Department of Community Medicine, UiT The Arctic University of Norway , Troms\u00f8 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8358-3226","authenticated-orcid":false,"given":"Erik W","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care Medicine, Surgical Clinic, Nordland Hospital , Bod\u00f8 ,","place":["Norway"]},{"name":"Institute of Clinical Medicine, UiT The Arctic University of Norway , Troms\u00f8 ,","place":["Norway"]},{"name":"Faculty of Nursing and Health Sciences, Nord University , Bod\u00f8 ,","place":["Norway"]},{"name":"Research Laboratory, Nordland Hospital Trust , Bod\u00f8 ,","place":["Norway"]},{"name":"Faculty of Medicine, Institute of Clinical Medicine, University of Oslo , Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5785-802X","authenticated-orcid":false,"given":"Tom Eirik","family":"Mollnes","sequence":"additional","affiliation":[{"name":"Research Laboratory, Nordland Hospital Trust , Bod\u00f8 ,","place":["Norway"]},{"name":"Faculty of Medicine, Institute of Clinical Medicine, University of Oslo , Oslo ,","place":["Norway"]},{"name":"Faculty of Health Sciences, K.G. Jebsen Thrombosis Research and Expertise Center, UiT The Arctic University of Norway , Troms\u00f8 ,","place":["Norway"]},{"name":"Department of Immunology, Oslo University Hospital and the University of Oslo , Oslo ,","place":["Norway"]},{"name":"Centre of Molecular Inflammation Research, Norwegian University of Science and Technology , Trondheim ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,1]]},"reference":[{"key":"2025022610323362900_r1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3390\/diagnostics7010005","article-title":"Air embolism: diagnosis, clinical management and outcomes","volume":"7","author":"McCarthy","year":"2017","journal-title":"Diagnostics (Basel)"},{"key":"2025022610323362900_r2","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/978-3-030-37323-8_42","volume-title":"Annual Update in Intensive Care and Emergency Medicine 2020.","author":"Heming","year":"2020"},{"key":"2025022610323362900_r3","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1046\/j.1475-097X.2003.00505.x","article-title":"Gas embolism: pathophysiology and treatment","volume":"23","author":"van Hulst","year":"2003","journal-title":"Clin. 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