Department of Anatomy, Histology and Embryology, Medical School, University of Ioannina, Ioannina, Greece.
Pathol Res Pract. 2010 Mar 15;206(3):145-50. doi: 10.1016/j.prp.2009.12.002. Epub 2010 Jan 22.
ARDS pathophysiology is characterized by complex mechanisms that involve cells of inflammation, lung tissue cells, cytokines, chemokines, as well as apoptosis activators and inhibitors. There are two important theories that link apoptosis with ARDS and suggest that epithelial cell apoptosis, as well as the accumulation of neutrophils in the lung, may contribute to a cascade of events and, finally, ARDS. The activation of the Fas/FasL pathway is an important mechanism of alveolar epithelial injury in the lungs of patients with ALI. In addition, neutrophilic inflammation in the alveolar spaces is characteristic of ALI in humans and in most animal models of ALI. The enhanced phagocytosis of apoptotic neutrophils could lead to resolution of inflammation and repair during ARDS. In this review, we will focus on elucidating the role of apoptosis in the pathophysiology of ARDS and the contribution of Fas-mediated inflammation in ARDS. Furthermore, we will give evidence that TNF-alpha, IL-1beta and IL-13 attenuate the pro-cell death effects of Fas/CD95 on A549 epithelial cells, at least partially, by the NF-kB and PI3-K pathways, suggesting that induction of the expression of antiapoptotic genes protects the epithelial cells from cell death.
ARDS 的病理生理学以涉及炎症细胞、肺组织细胞、细胞因子、趋化因子以及凋亡激活剂和抑制剂的复杂机制为特征。有两个重要理论将凋亡与 ARDS 联系起来，并表明上皮细胞凋亡以及中性粒细胞在肺部的积聚可能导致级联事件的发生，最终导致 ARDS。Fas/FasL 途径的激活是 ALI 患者肺上皮细胞损伤的重要机制。此外，肺泡空间中的中性粒细胞炎症是人类 ALI 和大多数 ALI 动物模型的特征。凋亡中性粒细胞的增强吞噬作用可能导致 ARDS 期间炎症的消退和修复。在这篇综述中，我们将重点阐明凋亡在 ARDS 病理生理学中的作用以及 Fas 介导的炎症在 ARDS 中的贡献。此外，我们将提供证据表明 TNF-α、IL-1β 和 IL-13 通过 NF-κB 和 PI3-K 途径至少部分减弱 Fas/CD95 对 A549 上皮细胞的促细胞死亡作用，这表明诱导抗凋亡基因的表达可保护上皮细胞免受细胞死亡。
