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    Neutrophil Extracellular Trap Formation and Syndecan-1 Shedding Are Increased After Trauma

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    Author
    Goswami, Julie
    MacArthur, Taleen
    Bailey, Kent
    Spears, Grant
    Kozar, Rosemary A
    Auton, Matthew
    Dong, Jing-Fei
    Key, Nigel S
    Heller, Stephanie
    Loomis, Erica
    Hall, Nathan W
    Johnstone, Andrea L
    Park, Myung S
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    Date
    2021-09
    Journal
    Shock (Augusta, Ga.)
    Publisher
    Wolters Kluwer Health
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1097/SHK.0000000000001741
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316482/
    Abstract
    Background: Damage-associated molecular patterns (DAMPs) stimulate endothelial syndecan-1 shedding and neutrophil extracellular traps (NET) formation. The role of NETs in trauma and trauma-induced hypercoagulability is unknown. We hypothesized that trauma patients with accelerated thrombin generation would have increased NETosis and syndecan-1 levels. Methods: In this pilot study, we analyzed 50 citrated plasma samples from 30 trauma patients at 0 h (n = 22) and 6 h (n = 28) from time of injury (TOI) and 21 samples from healthy volunteers, for a total of 71 samples included in analysis. Thrombin generation was quantified using calibrated automated thrombogram (CAT) and reported as lag time (LT), peak height (PH), and time to peak (ttPeak). Nucleosome calibrated (H3NUC) and free histone standardized (H3Free) ELISAs were used to quantify NETs. Syndecan-1 levels were quantified by ELISA. Results are presented as median [interquartile range] and Spearman rank correlations. Results: Plasma levels of H3NUC were increased in trauma patients as compared with healthy volunteers both at 0 h (89.8 ng/mL [35.4, 180.3]; 18.1 ng/mL [7.8, 37.4], P = 0.002) and at 6 h (86.5 ng/mL [19.2, 612.6]; 18.1 ng/mL [7.8, 37.4], P = 0.003) from TOI. H3Free levels were increased in trauma patients at 0 h (5.74 ng/mL [3.19, 8.76]; 1.61 ng/mL [0.66, 3.50], P = 0.002) and 6 h (5.52 ng/mL [1.46, 11.37]; 1.61 ng/mL [0.66, 3.50], P = 0.006). Syndecan-1 levels were greater in trauma patients (4.53 ng/mL [3.28, 6.28]; 2.40 ng/mL [1.66, 3.20], P < 0.001) only at 6 h from TOI. H3Free and syndecan-1 levels positively correlated both at 0 h (0.376, P = 0.013) and 6 h (0.583, P < 0.001) from TOI. H3NUC levels and syndecan-1 levels were positively correlated at 6 h from TOI (0.293, P = 0.041). TtPeak correlated inversely to H3 NUC (−0.358, P = 0.012) and syndecan-1 levels (−0.298, P = 0.038) at 6 h from TOI. Conclusions: Our pilot study demonstrates that trauma patients have increased NETosis, measured by H3NUC and H3Free levels, increased syndecan-1 shedding, and accelerated thrombin generation kinetics early after injury.
    Rights/Terms
    Copyright © 2021 by the Shock Society.
    Keyword
    endotheliopathy
    inflammation
    neutrophil extracellular traps
    syndecan-1
    thrombin
    trauma
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/16605
    ae974a485f413a2113503eed53cd6c53
    10.1097/SHK.0000000000001741
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