Air Bubbles Activate Complement and Trigger Hemostasis and C3-Dependent Cytokine Release Ex Vivo in Human Whole Blood

التفاصيل البيبلوغرافية
العنوان: Air Bubbles Activate Complement and Trigger Hemostasis and C3-Dependent Cytokine Release Ex Vivo in Human Whole Blood
المؤلفون: Dorte Christiansen, Corinna Lau, Trent M. Woodruff, Tonje Braaten, Benjamin S Storm, Hilde Fure, Judith K Ludviksen, Ole-Lars Brekke, John D. Lambris, Erik Waage Nielsen, Tom Eirik Mollnes
المصدر: Journal of Immunology
The Journal of Immunology Author Choice
بيانات النشر: American Association of Immunologists, 2021.
سنة النشر: 2021
مصطلحات موضوعية: Adult, Male, Hemostasis, Chemistry, medicine.medical_treatment, CD14, Immunology, Innate Immunity and Inflammation, Pharmacology, Middle Aged, Complement system, Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk immunologi: 716 [VDP], Tissue factor, Cytokine, Real-time polymerase chain reaction, medicine, Immunology and Allergy, Cytokines, Humans, Female, Ex vivo, Whole blood
الوصف: Key Points Air bubbles trigger a C3-driven thromboinflammation in human whole blood.Blocking C3, but not C5, attenuates the air-induced inflammation.Avoiding ambient air in test tubes attenuates thromboinflammation.
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, β-thromboglobulin 26-fold (all p < 0.05), and 25 cytokines 11-fold (range, 1.5–78-fold; all p < 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, 1.4–4.9-fold; all p < 0.05). C5 inhibition reduced PTF1+2 2-fold and TF-mRNA 12-fold (all p < 0.05). C5 or CD14 inhibition alone reduced three cytokines, including IL-1β (p = 0.02 and p = 0.03). Combined C3 and CD14 inhibition reduced all cytokines 3.9-fold (range, 1.3–9.5-fold; p < 0.003) and was most pronounced for IL-1β (3.2- versus 6.4-fold), IL-6 (2.5- versus 9.3-fold), IL-8 (4.9- versus 8.6-fold), and IFN-γ (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-1β release. These data have implications for future mechanistic studies and possible pharmacological interventions in patients with air embolism.
وصف الملف: application/pdf
اللغة: English
تدمد: 0022-1767
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7ad1192a17467f94749053936c42e4de
https://hdl.handle.net/11250/2984454
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....7ad1192a17467f94749053936c42e4de
قاعدة البيانات: OpenAIRE