本期胸小星将为大家带来免疫调节可溶HLA-G和HLA-E与肺移植术后CLAD恶化及HCMV升高相关；体外清除NETs可恢复废弃猪肺功能，一起来看看吧！
2017·EATTS
01
Laura M Kühner1, Sarah M Berger1, Mila Djinovic1, Philippe L Furlano1, Lisa M Steininger1, Anna-Lena Pirker1, Peter Jaksch2, Elisabeth Puchhammer-Stöckl1, Hannes Vietzen1
1 Center of Virology, Medical University Vienna, Vienna, Austria.
2 Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
Objective:
Plasma-soluble (s)HLA-G and sHLA-E are immunoregulatory proteins that balance the activation of NKG2A+ immune cells. In lung-transplant recipients (LTRs), dysregulated NKG2A+ natural killer cell responses may result in high-level human cytomegalovirus (HCMV) replication as well as chronic lung allograft dysfunction (CLAD), and especially the development of rapidly deteriorating CLAD is associated with high mortality.
Methods:
We thus analyzed the kinetics and function of sHLA-G and sHLA-E in follow-up samples of N = 76 LTRs to evaluate whether these immunoregulatory proteins are associated with the risk for CLAD and high-level HCMV replication.
Results: Here, we demonstrate that rapidly deteriorating CLAD LTRs are hallmarked by continually low (<107 ng/ml) sHLA-G levels. In contrast, high sHLA-E levels were associated with the subsequent development of high-level (>1,000 copies/ml) HCMV episodes.
Conclusion:
Thus, sHLA-G and sHLA-E may serve as novel biomarkers for the development of rapidly deteriorating CLAD and high-level HCMV replication in LTRs.
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免疫调节蛋白——可溶性HLA-G和HLA-E与肺移植术后慢性移植肺功能障碍的迅速恶化以及人巨细胞病毒血症相关
胸“星”外科学术团队兴趣小队成员 何贤 译
目的
方法
本研究对76例LTRs随访样本中sHLA-G和sHLA-E的动态变化及其生物学功能进行了分析，旨在评估这些免疫调节蛋白是否与CLAD和HCMV高水平复制的风险相关。
结果
结论
Figure 1. Kinetics and function of sHLA-G and sHLA-E in lung-transplant recipients (LTRs).
Figure 2. Impact of sHLA-E on the high-level viral replication in lung-transplant recipients (LTRs).
2017·EATTS
02
Restoring discarded porcine lungs by ex vivo removal of neutrophil extracellular traps
Margareta Mittendorfer1, Leif Pierre2, Tibor Huzevka1, Jeremy Schofield3, Simon T Abrams3, Guozheng Wang3, Cheng-Hock Toh4, Nicholas B Bèchet1, Ilma Caprnja1, Gunilla Kjellberg5, Andrew Aswani6, Franziska Olm1, Sandra Lindstedt1
1 Department of Clinical Sciences, Lund University, Lund, Sweden; Department of Cardiothoracic Surgery and Transplantation, Lund University Hospital, Lund, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden; Lund Stem Cell Centre, Lund University, Lund, Sweden.
2 Department of Cardiothoracic Surgery and Transplantation, Lund University Hospital, Lund, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden; Lund Stem Cell Centre, Lund University, Lund, Sweden.
3 Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, United Kingdom.
4 Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, United Kingdom; Roald Dahl Haemostasis & Thrombosis Centre, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom.
5 Department of Thoracic Surgery and Anaesthesiology, Uppsala University Hospital, Uppsala, Sweden.
6 Department of Critical Care, Guy's and St Thomas's NHS Foundation Trust, London, United Kingdom; Santersus AG, Zurich, Switzerland.
Background:
By causing inflammation and tissue damage, neutrophil extracellular traps (NETs) constitute an underlying mechanism of aspiration-induced lung injury, a major factor of the low utilization of donor lungs in lung transplantation (LTx).
Methods:
To determine whether NET removal during ex vivo lung perfusion (EVLP) can restore lung function and morphology in aspiration-damaged lungs, gastric aspiration lung injury was induced in 12 pigs. After confirmation of acute respiratory distress syndrome, the lungs were explanted and assigned to NET removal connected to EVLP (treated) (n = 6) or EVLP only (nontreated) (n = 6). Hemodynamic measurements were taken, and blood and tissue samples were collected to assess lung function, morphology, levels of cell-free DNA, extracellular histones, and nucleosomes as markers of NETs, as well as cytokine levels.
Results:
After EVLP and NET removal in porcine lungs, PaO2/FiO2 ratios increased significantly compared to those undergoing EVLP alone (P = 0.0411). Treated lungs had lower cell-free DNA (P = 0.0260) and lower levels of extracellular histones in EVLP perfusate (P = 0.0260) than nontreated lungs. According to histopathology, treated lungs showed less immune cell infiltration and less edema compared with nontreated lungs, which was reflected in decreased levels of proinflammatory cytokines in EVLP perfusate and bronchoalveolar lavage fluid.
Conclusions:
To conclude, removing NETs during EVLP improved lung function and morphology in aspiration-damaged donor lungs. The ability to remove NETs during EVLP could represent a new therapeutic approach for LTx and potentially expand the donor pool for transplantation.
[CITATION]: Margareta Mittendorfer, Leif Pierre, Tibor Huzevka, et al. Restoring discarded porcine lungs by ex vivo removal of neutrophil extracellular traps. J Heart Lung Transplant. 2024 Jul 20:S1053-2498(24)01736-4.
[DOI]: 10.1016/j.healun.2024.07.007.
[IF]: 6.4
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肺移植前Th2免疫反应的循环指标变化与原发性移植物失功减少相关
胸“星”外科学术团队兴趣小队成员 龚静怡 译
背景
方法
结果
结论
Figure 2. Establishment of acute lung injury following gastric aspiration.
Figure 4. Ex vivo lung perfusion (EVLP) with neutrophil extracellular trap removal improved hemodynamic parameters and lung morphology.
2017·EATTS
