Guangxi Clinical Research Center for Anesthesiology, Nanning 530021, PR China; Department of Breast and Thyroid Surgery, South China Hospital, Medical School, Shenzhen University, Shenzhen 518116, PR China.
Guangxi Engineering Research Center for Tissue & Organ Injury and Repair Medicine, Nanning 530021, PR China; Guangxi Health Commission Key Laboratory of Basic Science and Prevention of Perioperative Organ Disfunction, Nanning 530021, PR China; Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning 530021, PR China; Department of Critical Medicine, Guangxi Medical University Cancer Hospital, Nanning 530021, PR China.
Int Immunopharmacol. 2024 Dec 5;142(Pt A):112997. doi: 10.1016/j.intimp.2024.112997. Epub 2024 Aug 31.
Ventilation is the main respiratory support therapy for acute respiratory distress syndrome, which triggers acute lung injury (ALI). Macrophage polarization is vital for the resolution of inflammation and tissue injury. We hypothesized that transforming growth factor (TGF)-β1 may attenuate inflammation and ventilator-induced ALI by promoting M2 macrophage polarization.
C57BL/6 mice received 4-hour ventilation and extubation to observe the resolution of lung injury and inflammation. Lung vascular permeability, inflammation, and histological changes in the lungs were evaluated by bronchoalveolar lavage analysis, enzyme linked immunosorbent assay, hematoxylin and eosin staining, as well as transmission electron microscope. TGF-β1 cellular production and macrophage subsets were analyzed by flow cytometry. The relative expressions of targeted proteins and genes were measured by immunofuorescence staining, Western blot, and quantitative polymerase chain reaction.
High tidal volume-induced injury and inflammation were resolved at 3 days of post-ventilation (PV3d) to PV10d, with increased elastic fibers, proteoglycans, and collagen content, as well as higher TGF-β1 levels. M1 macrophages were increased in the acute phase, whereas M2a macrophages began to increase from PV1d to PV3d, as well as increased M2c macrophages from PV3d to PV7d. A single dose of rTGF-β1 attenuated lung injury and inflammation at end of ventilation with polymorphonuclear leukocyte apoptosis, while nTAb pretreatment induced the abnormal elevation of TGF-β1 that aggravated lung injury and inflammation due to the significant inhibition of M1 macrophages polarized to M2a, M2b, and M2c macrophages.
Precise secretion of TGF-β1-mediated macrophage polarization plays a crucial role in the resolution of ventilator-induced inflammatory lung injury.
通气是急性呼吸窘迫综合征（ARDS）的主要呼吸支持治疗方法，它会引发急性肺损伤（ALI）。巨噬细胞极化对于炎症和组织损伤的解决至关重要。我们假设转化生长因子（TGF）-β1 可能通过促进 M2 巨噬细胞极化来减轻炎症和呼吸机诱导的 ALI。
C57BL/6 小鼠接受 4 小时通气和拔管，以观察肺损伤和炎症的消退情况。通过支气管肺泡灌洗分析、酶联免疫吸附试验、苏木精和伊红染色以及透射电子显微镜评估肺血管通透性、炎症和肺组织学变化。通过流式细胞术分析 TGF-β1 细胞产生和巨噬细胞亚群。通过免疫荧光染色、Western blot 和定量聚合酶链反应测量靶向蛋白和基因的相对表达。
高容量通气诱导的损伤和炎症在通气后 3 天（PV3d）至 10 天（PV10d）得到解决，弹性纤维、糖胺聚糖和胶原蛋白含量增加，TGF-β1 水平升高。急性期 M1 巨噬细胞增加，而从 PV1d 到 PV3d，M2a 巨噬细胞开始增加，从 PV3d 到 PV7d，M2c 巨噬细胞增加。单次给予 rTGF-β1 可在通气结束时减轻肺损伤和炎症，同时促进多形核白细胞凋亡，而 nTAb 预处理诱导 TGF-β1 的异常升高，由于对 M1 巨噬细胞向 M2a、M2b 和 M2c 巨噬细胞的极化的显著抑制，导致肺损伤和炎症加重。
TGF-β1 介导的巨噬细胞极化的精确分泌在呼吸机诱导的炎症性肺损伤的解决中起着关键作用。
