TY - JOUR
T1 - Neutrophil Extracellular Trap Formation and Syndecan-1 Shedding Are Increased after Trauma
AU - Goswami, Julie
AU - Macarthur, Taleen
AU - Bailey, Kent
AU - Spears, Grant
AU - Kozar, Rosemary A.
AU - Auton, Matthew
AU - Dong, Jing Fei
AU - Key, Nigel S.
AU - Heller, Stephanie
AU - Loomis, Erica
AU - Hall, Nathan W.
AU - Johnstone, Andrea L.
AU - Park, Myung S.
N1 - Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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 0h (n=22) and 6h (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 0h (89.8ng/mL [35.4, 180.3]; 18.1ng/mL [7.8, 37.4], P=0.002) and at 6h (86.5ng/mL [19.2, 612.6]; 18.1ng/mL [7.8, 37.4], P=0.003) from TOI. H3Free levels were increased in trauma patients at 0h (5.74ng/mL [3.19, 8.76]; 1.61ng/mL [0.66, 3.50], P=0.002) and 6h (5.52ng/mL [1.46, 11.37]; 1.61ng/mL [0.66, 3.50], P=0.006). Syndecan-1 levels were greater in trauma patients (4.53ng/mL [3.28, 6.28]; 2.40ng/mL [1.66, 3.20], P<0.001) only at 6h from TOI. H3Free and syndecan-1 levels positively correlated both at 0h (0.376, P=0.013) and 6h (0.583, P<0.001) from TOI. H3NUC levels and syndecan-1 levels were positively correlated at 6h 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 6h 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.
AB - 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 0h (n=22) and 6h (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 0h (89.8ng/mL [35.4, 180.3]; 18.1ng/mL [7.8, 37.4], P=0.002) and at 6h (86.5ng/mL [19.2, 612.6]; 18.1ng/mL [7.8, 37.4], P=0.003) from TOI. H3Free levels were increased in trauma patients at 0h (5.74ng/mL [3.19, 8.76]; 1.61ng/mL [0.66, 3.50], P=0.002) and 6h (5.52ng/mL [1.46, 11.37]; 1.61ng/mL [0.66, 3.50], P=0.006). Syndecan-1 levels were greater in trauma patients (4.53ng/mL [3.28, 6.28]; 2.40ng/mL [1.66, 3.20], P<0.001) only at 6h from TOI. H3Free and syndecan-1 levels positively correlated both at 0h (0.376, P=0.013) and 6h (0.583, P<0.001) from TOI. H3NUC levels and syndecan-1 levels were positively correlated at 6h 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 6h 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.
KW - Endotheliopathy
KW - inflammation
KW - neutrophil extracellular traps
KW - syndecan-1
KW - thrombin
KW - trauma
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U2 - 10.1097/SHK.0000000000001741
DO - 10.1097/SHK.0000000000001741
M3 - Article
C2 - 33534396
AN - SCOPUS:85114385989
SN - 1073-2322
VL - 56
SP - 433
EP - 439
JO - Shock
JF - Shock
IS - 3
ER -