Neutrophil Extracellular Trap Formation and Syndecan-1 Shedding Are Increased After Trauma.
Neutrophil Extracellular Trap Formation and Syndecan-1 Shedding Are Increased After Trauma.
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DOI：
10.1097/shk.0000000000001741
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发表时间：
2021-09-01
期刊：
影响因子：
--
通讯作者：
Park MS
中科院分区：
文献类型：
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作者：
Goswami J;MacArthur T;Bailey K;Spears G;Kozar RA;Auton M;Dong JF;Key NS;Heller S;Loomis E;Hall NW;Johnstone AL;Park MS
损伤相关分子模式（DAMP）刺激内皮syndecan-1脱落和中性粒细胞细胞外陷阱（NET）形成。NET在创伤和创伤诱导的高凝状态中的作用尚不清楚。我们假设创伤患者凝血酶生成加快，NETosis和syndecan-1水平升高。在这项初步研究中，我们分析了30名创伤患者在受伤时间（TOI）0 h（n=22）和6 h（n=28）时的50份柠檬酸盐血浆样本以及21份健康志愿者样本，共71份样本纳入分析。使用校准的自动血栓图（CAT）定量凝血酶生成，并报告为滞后时间（LT）、峰高（PH）和达峰时间（ttPeak）。使用核小体校准（H3 NUC）和游离组蛋白标准化（H3 Free）ELISA来定量NET。通过ELISA定量多配体蛋白聚糖-1水平。结果以中位数[四分位距]和斯皮尔曼等级相关表示。与健康志愿者相比，创伤患者中H3 NUC的血浆水平在TOI 0小时（89.8 ng/mL [35.4，180.3]; 18.1 ng/mL [7.8，37.4]，p=0.002）和6小时（86.5 ng/mL [19.2，612.6]; 18.1 ng/mL [7.8，37.4]，p=0.003）均增加。创伤患者在0 h（5.74 ng/mL [3.19，8.76]; 1.61 ng/mL [0.66，3.50]，p=0.002）和6 h（5.52 ng/mL [1.46，11.37]; 1.61 ng/mL [0.66，3.50]，p=0.006）时的H3游离水平升高。创伤患者中Syndecan-1水平仅在TOI后6小时更高（4.53 ng/mL [3.28，6.28]; 2.40 ng/mL [1.66，3.20]，p<0.001）。在TOI后0 h（0.376，p=0.013）和6 h（0.583，p<0.001），H3游离和多配体蛋白聚糖-1水平均呈正相关。H3 NUC水平和多配体蛋白聚糖-1水平在TOI后6小时呈正相关（0.293，p=0.041）。TtPeak与TOI后6小时的H3 NUC（-0.358，p=0.012）和syndecan-1水平（-0.298，p=0.038）呈负相关。我们的初步研究表明，创伤患者在损伤后早期具有增加的NETosis（通过H3 NUC和H3 Free水平测量）、增加的syndecan-1脱落和加速的凝血酶生成动力学。
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. 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. Plasma levels of H3NUC were increased in trauma patients as compared to healthy volunteers both at 0h (89.8 ng/mL [35.4, 180.3]; 18.1 ng/mL [7.8, 37.4], p=0.002) and at 6h (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 0h (5.74 ng/mL [3.19, 8.76]; 1.61 ng/mL [0.66, 3.50], p=0.002) and 6h (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 6h from TOI. H3Free and syndecan-1 levels positively correlated both at Oh (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. 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.