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RAGE-induced ILC2 expansion in acute lung injury due to haemorrhagic shock.

RAGE诱导的ILC2在失血性休克引起的急性肺损伤中扩张。

  • 影响因子:4.63
  • DOI:10.1136/thoraxjnl-2019-213613
  • 作者列表:"Zhang K","Jin Y","Lai D","Wang J","Wang Y","Wu X","Scott M","Li Y","Hou J","Billiar T","Wilson M","Shu Q","Fang X","Fan J
  • 发表时间:2020-03-01
Abstract

BACKGROUND:Type 2 immune dysfunction contributes to acute lung injury and lethality following haemorrhagic shock (HS) and trauma. Group 2 innate lymphoid cells (ILC2s) play a significant role in the regulation of type 2 immune responses. However, the role of ILC2 in post-HS acute lung injury and the underlying mechanism has not yet been elucidated. OBJECTIVE:To investigate the regulatory role of ILC2s in HS-induced acute lung injury and the underlying mechanism in patients and animal model. METHODS:Circulating markers of type 2 immune responses in patients with HS and healthy controls were characterised. Using a murine model of HS, the role of high-mobility group box 1 (HMGB1)-receptor for advanced glycation end products (RAGE) signalling in regulation of ILC2 proliferation, survival and function was determined. And the role of ILC2 in inducing type 2 immune dysfunction was assessed as well. RESULTS:The number of ILC2s was significantly increased in the circulation of patients with HS that was correlated with the increase in the markers of type 2 immune responses in the patients. Animal studies showed that HMGB1 acted via RAGE to induce ILC2 accumulation in the lungs by promoting ILC2 proliferation and decreasing ILC2 death. The expansion of ILC2s resulted in type 2 cytokines secretion and eosinophil infiltration in the lungs, both of which contributed to lung injury after HS. CONCLUSIONS:These results indicate that HMGB1-RAGE signalling plays a critical role in regulating ILC2 biological function that aggravates type 2 lung inflammation following HS.

摘要

背景: 2型免疫功能紊乱导致失血性休克 (HS) 和创伤后的急性肺损伤和死亡。第2组固有淋巴样细胞 (ILC2s) 在调节2型免疫应答中起重要作用。然而,ILC2在HS后急性肺损伤中的作用和潜在机制尚未阐明。 目的: 探讨ILC2s在HS诱导的急性肺损伤中的调节作用及其机制。 方法: 对HS患者和健康对照的2型免疫反应的循环标志物进行表征。使用HS的小鼠模型,确定了高迁移率族蛋白b1 (HMGB1)-晚期糖基化终产物受体 (RAGE) 信号在ILC2增殖、存活和功能调节中的作用。并评估ILC2在诱导2型免疫功能障碍中的作用。 结果: HS患者循环中ILC2s的数量显著增加,这与患者2型免疫反应标志物的增加相关。动物研究表明,HMGB1通过RAGE通过促进ILC2增殖和减少ILC2死亡来诱导ILC2在肺中的积累。ILC2s的扩张导致2型细胞因子分泌和肺内嗜酸性粒细胞浸润,这两者均导致HS后肺损伤。 结论: 这些结果表明HMGB1-RAGE信号在调节ILC2生物学功能中起关键作用,ILC2生物学功能加重HS后的2型肺部炎症。

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DOI:10.1097/TA.0000000000002498
作者列表:["Williams J","Merutka N","Meyer D","Bai Y","Prater S","Cabrera R","Holcomb JB","Wade CE","Love JD","Cotton BA"]

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影响因子:1.33
发表时间:2020-01-01
DOI:10.3233/CH-180541
作者列表:["Chayer B","Allard L","Qin Z","Garcia-Duitama J","Roger L","Destrempes F","Cailhier JF","Denault A","Cloutier G"]

METHODS:BACKGROUND:An enhanced inflammatory response is a trigger to the production of blood macromolecules involved in abnormally high levels of erythrocyte aggregation. OBJECTIVE:This study aimed at demonstrating for the first time the clinical feasibility of a non-invasive ultrasound-based erythrocyte aggregation quantitative measurement method for potential application in critical care medicine. METHODS:Erythrocyte aggregation was evaluated using modeling of the backscatter coefficient with the Structure Factor Size and Attenuation Estimator (SFSAE). SFSAE spectral parameters W (packing factor) and D (mean aggregate diameter) were measured within the antebrachial vein of the forearm and tibial vein of the leg in 50 healthy participants at natural flow and reduced flow controlled by a pressurized bracelet. Blood samples were also collected to measure erythrocyte aggregation ex vivo with an erythroaggregometer (parameter S10). RESULTS:W and Din vivo measurements were positively correlated with the ex vivoS10 index for both measurement sites and shear rates (correlations between 0.35-0.81, p < 0.05). Measurement at low shear rate was found to increase the sensitivity and reliability of this non-invasive measurement method. CONCLUSIONS:We behold that the SFSAE method presents systemic measures of the erythrocyte aggregation level, since results on upper and lower limbs were highly correlated.

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影响因子:2.27
发表时间:2020-02-01
DOI:10.1213/ANE.0000000000004419
作者列表:["Takeshita S","Tanaka KA","Sawa T","Sanda M","Mizobe T","Ogawa S"]

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血液检测可分为血液一般检测、溶血性贫血的实验室检测、骨髓细胞学检测、血型鉴定与交叉配血试验。可以检测出常见血液病的血液学持征。

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