Introduction: We previously reported that extracellular vesicles (EVs) released during Escherichia coli bacterial pneumonia were inflammatory, and administration of high molecular weight hyaluronic acid (HMW HA) suppressed several indices of acute lung injury (ALI) from Escherichia coli 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 Pseudomonas aeruginosa (PA)103 bacterial pneumonia. Methods: For lungs with baseline alveolar fluid clearance (AFC)<10%/h, HMW HA 1 or 2 mg was injected intravenously after 1 h (N = 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 (N = 6). In vitro experiments were conducted to evaluate the effects of HA on inflammation and bacterial phagocytosis. Results: 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. Discussion: In the presence of impaired alveolar epithelial transport capacity, administration of HMW HA improved the resolution of pulmonary edema from Pseudomonas PA103 bacterial pneumonia.

中文翻译：

---

高分子量透明质酸对体外灌注人肺中严重铜绿假单胞菌肺炎的治疗作用

引言：我们之前报道过大肠杆菌细菌性肺炎期间释放的细胞外囊泡 (EVs) 具有炎症性，而高分子量透明质酸 (HMW HA) 的施用通过与这些结合抑制了大肠杆菌肺炎引起的急性肺损伤 (ALI) 的几个指标炎症 EV。目前的研究旨在研究 HMW HA 在体外灌注的铜绿假单胞菌 (PA)103 细菌性肺炎损伤的人肺中的治疗效果。方法：对于基线肺泡液清除率（AFC）<10%/h 的肺，1 h 后静脉注射 HMW HA 1 或 2 mg（N = 4-9），并从灌注液中收集 PA 肺炎期间释放的 EV。 6小时。对于基线 AFC>10%/h 的肺，1 小时后静脉注射 HMW HA 2 mg（N = 6）。进行体外实验以评估 HA 对炎症和细菌吞噬作用的影响。结果：对于 AFC<10%/h 的肺，静脉注射 HMW HA 可显着恢复 AFC，并在数字上降低 PA103 肺炎引起的蛋白质通透性和肺泡炎症，但对 6 小时的细菌计数没有影响。然而，HMW HA 改善了人类单核细胞和中性粒细胞的细菌吞噬作用，并抑制了肺炎期间释放的 EV 对单核细胞的炎症特性。对于 AFC>10%/h 的肺，静脉注射 HMW HA 可改善 PA103 肺炎的 AFC，但对蛋白质通透性、炎症或细菌计数没有显着影响。讨论：在肺泡上皮转运能力受损的情况下，