Geiser Thomas
Division of Pulmonary Medicine, Department of Clinical Research, Inselspital, Bern.
Swiss Med Wkly. 2003 Nov 22;133(43-44):586-90. doi: 10.4414/smw.2003.10267.
In patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), extensive damage to the alveolar epithelial and endothelial barrier is observed, resulting in the influx of protein-rich oedema fluid into the air spaces. Efficient alveolar epithelial repair is crucial to ALI/ARDS patients' recovery. Future therapeutic strategies may therefore include acceleration of the epithelial repair process in the injured lung. However, a better understanding of the cellular and molecular mechanisms that promote alveolar epithelial repair is needed if novel therapeutic strategies are to be developed. Pulmonary oedema fluid from patients with ALI/ARDS and from patients with hydrostatic oedema as control was obtained, and the effect on alveolar epithelial repair in vitro using our alveolar epithelial wound repair bioassay was studied. In contrast to the initial hypothesis, pulmonary oedema fluid from ALI/ARDS patients increased alveolar epithelial repair in vitro by an interleukin-1beta (IL-1beta)-dependent mechanism, demonstrating a novel, possibly beneficial role for IL-1beta in patients with ALI/ARDS. Further studies using primary alveolar epithelial cells from rats revealed that IL-1beta induced alveolar epithelial repair by an epidermal growth factor (EGF)/transforming growth factor-alpha (TGF-alpha)-dependent pathway. Besides EGF and TGF-alpha, keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF)--both present in pulmonary oedema fluid obtained from patients with ALI/ARDS--stimulate alveolar epithelial repair in vitro. Further experimental and clinical studies will show whether acceleration of alveolar epithelial repair by modulating cytokines and growth factors in the injured lung represents a promising new therapeutic strategy in patients with ALI/ARDS.
在急性肺损伤（ALI）或急性呼吸窘迫综合征（ARDS）患者中，可观察到肺泡上皮和内皮屏障受到广泛损伤，导致富含蛋白质的水肿液流入气腔。有效的肺泡上皮修复对ALI/ARDS患者的康复至关重要。因此，未来的治疗策略可能包括加速受损肺组织中的上皮修复过程。然而，若要开发新的治疗策略，就需要更好地了解促进肺泡上皮修复的细胞和分子机制。获取了ALI/ARDS患者以及作为对照的静水压性水肿患者的肺水肿液，并使用我们的肺泡上皮伤口修复生物测定法研究了其对体外肺泡上皮修复的影响。与最初的假设相反，ALI/ARDS患者的肺水肿液通过白细胞介素-1β（IL-1β）依赖性机制在体外增加了肺泡上皮修复，这表明IL-1β在ALI/ARDS患者中具有一种新的、可能有益的作用。使用大鼠原代肺泡上皮细胞进行的进一步研究表明，IL-1β通过表皮生长因子（EGF）/转化生长因子-α（TGF-α）依赖性途径诱导肺泡上皮修复。除了EGF和TGF-α外，角质形成细胞生长因子（KGF）和肝细胞生长因子（HGF）（二者均存在于从ALI/ARDS患者获取的肺水肿液中）在体外刺激肺泡上皮修复。进一步的实验和临床研究将表明，通过调节受损肺组织中的细胞因子和生长因子来加速肺泡上皮修复是否代表了ALI/ARDS患者一种有前景的新治疗策略。
