Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Departments of Anesthesiology, Medicine, and Cardiovascular Research Institute, University of California, San Francisco, California.
Am J Physiol Lung Cell Mol Physiol. 2021 Nov 1;321(5):L827-L836. doi: 10.1152/ajplung.00626.2020. Epub 2021 Sep 15.
We previously reported that extracellular vesicles (EVs) released during () bacterial pneumonia were inflammatory, and administration of high molecular weight hyaluronic acid (HMW HA) suppressed several indices of acute lung injury (ALI) from pneumonia by binding to these inflammatory EVs. The current study was undertaken to study the therapeutic effects of HMW HA in ex vivo perfused human lungs injured with (PA)103 bacterial pneumonia. For lungs with baseline alveolar fluid clearance (AFC) <10%/h, HMW HA 1 or 2 mg was injected intravenously after 1 h ( = 4-9), and EVs released during PA pneumonia were collected from the perfusate over 6 h. For lungs with baseline AFC > 10%/h, HMW HA 2 mg was injected intravenously after 1 h ( = 6). In vitro experiments were conducted to evaluate the effects of HA on inflammation and bacterial phagocytosis. For lungs with AFC < 10%/h, administration of HMW HA intravenously significantly restored AFC and numerically decreased protein permeability and alveolar inflammation from PA103 pneumonia but had no effect on bacterial counts at 6 h. However, HMW HA improved bacterial phagocytosis by human monocytes and neutrophils and suppressed the inflammatory properties of EVs released during pneumonia on monocytes. For lungs with AFC > 10%/h, administration of HMW HA intravenously improved AFC from PA103 pneumonia but had no significant effects on protein permeability, inflammation, or bacterial counts. In the presence of impaired alveolar epithelial transport capacity, administration of HMW HA improved the resolution of pulmonary edema from PA103 bacterial pneumonia.
我们之前报道过，（）细菌性肺炎期间释放的细胞外囊泡（EVs）具有炎症性，而高相对分子质量透明质酸（HMWHA）通过与这些炎症性 EVs 结合，抑制了由（）肺炎引起的急性肺损伤（ALI）的几个指标。本研究旨在研究 HMWHA 在体外灌注的人类肺部中治疗（）肺炎的效果。对于基础肺泡液清除率（AFC）<10%/h 的肺，在 1 h 后（n = 4-9）静脉注射 HMWHA1 或 2mg，并在 6 h 内从灌流液中收集（）肺炎期间释放的 EVs。对于基础 AFC>10%/h 的肺，在 1 h 后（n = 6）静脉注射 HMWHA2mg。进行体外实验以评估 HA 对炎症和细菌吞噬作用的影响。对于 AFC<10%/h 的肺，静脉内给予 HMWHA 可显著恢复 AFC，并在数值上降低由（）肺炎引起的蛋白质通透性和肺泡炎症，但对 6 h 时的细菌计数没有影响。然而，HMWHA 可改善人单核细胞和中性粒细胞对细菌的吞噬作用，并抑制肺炎期间释放的 EVs 对单核细胞的炎症特性。对于 AFC>10%/h 的肺，静脉内给予 HMWHA 可改善（）肺炎引起的 AFC，但对蛋白质通透性、炎症或细菌计数无显著影响。在肺泡上皮转运能力受损的情况下，给予 HMWHA 可改善由（）肺炎引起的肺水肿的消退。
