中性粒细胞胞外陷阱形成和 syndecan-1 的脱落在外伤后增加。
Neutrophil Extracellular Trap Formation and Syndecan-1 Shedding Are Increased After Trauma.
机构信息
Division of Trauma, Critical Care, and General Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota.
Division of Clinical Statistics and Biostatistics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
出版信息
Shock. 2021 Sep 1;56(3):433-439. doi: 10.1097/SHK.0000000000001741.
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.
背景
损伤相关分子模式（DAMPs）可刺激内皮细胞硫酸乙酰肝素蛋白聚糖-1 脱落和中性粒细胞胞外诱捕网（NET）的形成。NET 在创伤和创伤引起的高凝状态中的作用尚不清楚。我们假设，发生加速性凝血酶生成的创伤患者将有更高的 NETosis 和硫酸乙酰肝素蛋白聚糖-1 水平。
方法
在这项初步研究中，我们分析了 30 名创伤患者在损伤后 0 小时（n=22）和 6 小时（n=28）以及 21 名健康志愿者的 50 份枸橼酸盐血浆样本，共分析了 71 份样本。使用校准自动血栓生成图（CAT）定量测定凝血酶生成，并报告为延迟时间（LT）、峰值高度（PH）和达到峰值时间（ttPeak）。使用核小体校准（H3NUC）和游离组蛋白标准化（H3Free）ELISA 定量测定 NET。通过 ELISA 定量测定硫酸乙酰肝素蛋白聚糖-1 水平。结果表示为中位数[四分位距]和 Spearman 秩相关。
结果
与健康志愿者相比，创伤患者的 H3NUC 水平在损伤后 0 小时（89.8ng/ml[35.4，180.3]；18.1ng/ml[7.8，37.4]，P=0.002）和 6 小时（86.5ng/ml[19.2，612.6]；18.1ng/ml[7.8，37.4]，P=0.003）时均升高。创伤患者的 H3Free 水平在损伤后 0 小时（5.74ng/ml[3.19，8.76]；1.61ng/ml[0.66，3.50]，P=0.002）和 6 小时（5.52ng/ml[1.46，11.37]；1.61ng/ml[0.66，3.50]，P=0.006）时也升高。只有在损伤后 6 小时，创伤患者的硫酸乙酰肝素蛋白聚糖-1 水平（4.53ng/ml[3.28，6.28]；2.40ng/ml[1.66，3.20]，P<0.001）更高。在损伤后 0 小时（0.376，P=0.013）和 6 小时（0.583，P<0.001），H3Free 和硫酸乙酰肝素蛋白聚糖-1 水平呈正相关。在损伤后 6 小时，H3NUC 水平与硫酸乙酰肝素蛋白聚糖-1 水平呈正相关（0.293，P=0.041）。ttPeak 与 H3 NUC（-0.358，P=0.012）和损伤后 6 小时的硫酸乙酰肝素蛋白聚糖-1 水平（-0.298，P=0.038）呈负相关。
结论
我们的初步研究表明，创伤患者在损伤后早期即出现 NETosis 增加，表现为 H3NUC 和 H3Free 水平升高、硫酸乙酰肝素蛋白聚糖-1 脱落增加和凝血酶生成动力学加速。
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