Air Bubbles Activate Complement and Trigger Hemostasis and C3-Dependent Cytokine Release Ex Vivo in Human Whole Blood
Permanent lenke
https://hdl.handle.net/10037/23902Dato
2021-11-03Type
Journal articleTidsskriftartikkel
Peer reviewed
Forfatter
Storm, Benjamin; Christiansen, Dorte; Fure, Hilde; Ludviksen, Judith K; Lau, Corinna; Lambris, John D.; Woodruff, Trent M.; Brekke, Ole-Lars; Braaten, Tonje Bjørndal; Nielsen, Erik Waage; Mollnes, Tom EirikSammendrag
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, b-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-1b (p 5 0.02 and p 5 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-1b (3.2- versus 6.4-fold), IL-6 (2.5-
versus 9.3-fold), IL-8 (4.9- versus 8.6-fold), and IFN-g (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-1b release. These data have implications for future mechanistic studies and possible pharmacological
interventions in patients with air embolism.
Er en del av
Storm, B. (2022). Venous Air Embolism and Complement-driven Thromboinflammation. In vitro human whole blood studies and in vivo porcine studies on the effect of air emboli on the complement system, cytokine network, and the hemostasis. (Doctoral thesis). https://hdl.handle.net/10037/25922.Forlag
American Association of ImmunologistsSitering
Storm BS, Christiansen D, Fure H, Ludviksen JK, Lau C, Lambris JD, Woodruff TM, Brekke O.L., Braaten T, Nielsen EW, Mollnes TE. Air Bubbles Activate Complement and Trigger Hemostasis and C3-Dependent Cytokine Release Ex Vivo in Human Whole Blood. Journal of Immunology. 2021;207(11):2828-2840Metadata
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