Ehrentraut Heidi, Weisheit Christina, Scheck Marcel, Frede Stilla, Hilbert Tobias
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
J Inflamm (Lond). 2018 Jun 14;15:12. doi: 10.1186/s12950-018-0188-5. eCollection 2018.
Breakdown of the alveolo-capillary wall is pathognomonic for Acute Lung Injury (ALI). Angiopoietins, vascular-specific growth factors, are linked to endothelial barrier dysfunction, and elevated Angiopoietin-2 (ANG2) levels are associated with poor outcome of ALI patients. Specialized immune cells, referred to as 'TIE2-expressing monocytes and macrophages' (TEM), were shown to specifically respond to ANG2 binding. However, their involvement in acute inflammatory processes is so far completely undescribed. Thus, our aim was to assess the dynamics of TEMs in a murine model of ALI.
Intratracheal instillation of LPS induced a robust pulmonary pro-inflammatory response with endothelial barrier dysfunction and significantly enhanced ANG2 expression. The percentage number of TEMs, assessed by FACS analysis, was more than trebled compared to controls, with TEM count in lungs reaching more than 40% of all macrophages. Such distinct dynamic was absent in all other analyzed compartments (alveolar space, spleen, blood). Incubation of the monocytic cell line THP-1 with LPS or TNF-α resulted in a dose-dependent, significant upregulation of TIE2, suggesting that not recruitment from extra-pulmonary compartments but TIE2 upregulation in resident macrophages accounts for increased lung TEM frequencies.
For the first time, our data provide evidence that the activity of TEMs changes at sites of acute inflammation.
肺泡-毛细血管壁的破坏是急性肺损伤（ALI）的特征性表现。血管生成素是血管特异性生长因子，与内皮屏障功能障碍有关，血管生成素-2（ANG2）水平升高与ALI患者的不良预后相关。一种被称为“表达TIE2的单核细胞和巨噬细胞”（TEM）的特殊免疫细胞已被证明对ANG2结合有特异性反应。然而，它们在急性炎症过程中的作用至今尚未完全阐明。因此，我们的目的是评估ALI小鼠模型中TEM的动态变化。
气管内注入脂多糖（LPS）可引发强烈的肺部促炎反应，伴有内皮屏障功能障碍，并显著增强ANG2表达。通过流式细胞术分析评估，TEM的百分比数量与对照组相比增加了两倍多，肺部的TEM计数达到所有巨噬细胞的40%以上。在所有其他分析的部位（肺泡腔、脾脏、血液）均未观察到这种明显的动态变化。用LPS或肿瘤坏死因子-α（TNF-α）孵育单核细胞系THP-1导致TIE2呈剂量依赖性显著上调，这表明肺部TEM频率增加并非源于肺外部位的募集，而是源于驻留巨噬细胞中TIE2的上调。
我们的数据首次提供了证据，表明TEM的活性在急性炎症部位会发生变化。
