Vlahakis N E, Schroeder M A, Limper A H, Hubmayr R D
Thoracic Diseases Research Unit, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Am J Physiol. 1999 Jul;277(1):L167-73. doi: 10.1152/ajplung.1999.277.1.L167.
Mechanical ventilation can injure the lung, causing edema and alveolar inflammation. Interleukin-8 (IL-8) plays an important role in this inflammatory response. We postulated that cyclic cell stretch upregulates the production and release of IL-8 by human alveolar epithelium in the absence of structural cell damage or paracrine stimulation. To test this hypothesis, alveolar epithelial cells (A549 cells) were cultured on a deformable silicoelastic membrane. When stretched by 30% for up to 48 h, the cells released 49 +/- 34% more IL-8 (P < 0.001) than static controls. Smaller deformations (20% stretch) produced no consistent increase in IL-8. Stretch of 4 h duration increased IL-8 gene transcription fourfold above baseline. Stretch had no effect on cell proliferation, cell viability as assessed by (51)Cr release assay, or the release of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha. We conclude that deformation per se can trigger inflammatory signaling and that alveolar epithelial cells may be active participants in the alveolitis associated with ventilator-induced lung injury.
机械通气可损伤肺脏，导致肺水肿和肺泡炎症。白细胞介素-8（IL-8）在这种炎症反应中起重要作用。我们推测，在不存在结构细胞损伤或旁分泌刺激的情况下，周期性细胞拉伸可上调人肺泡上皮细胞IL-8的产生和释放。为验证这一假设，将肺泡上皮细胞（A549细胞）培养在可变形的硅弹性膜上。当拉伸30%长达48小时时，细胞释放的IL-8比静态对照多49±34%（P<0.001）。较小的变形（20%拉伸）未使IL-8持续增加。4小时的拉伸使IL-8基因转录比基线水平增加了四倍。拉伸对细胞增殖、通过（51）Cr释放试验评估的细胞活力，或粒细胞-巨噬细胞集落刺激因子和肿瘤坏死因子-α的释放均无影响。我们得出结论，变形本身可触发炎症信号，肺泡上皮细胞可能是与呼吸机诱导的肺损伤相关的肺泡炎的积极参与者。
