Institute of Physiology and Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
Clin Exp Immunol. 2010 Aug;161(2):324-31. doi: 10.1111/j.1365-2249.2010.04175.x. Epub 2010 May 7.
Apoptotic cell death has been considered an underlying mechanism in acute lung injury. To evaluate the evidence of this process, apoptosis rate was determined in effector cells (alveolar macrophages, neutrophils) and target cells (tracheobronchial and alveolar epithelial cells) of the respiratory compartment upon exposure to hypoxia and endotoxin stimulation in vitro. Cells were exposed to 5% oxygen or incubated with lipopolysaccharide (LPS) for 4, 8 and 24 h, and activity of caspase-3, -8 and -9 was determined. Caspase-3 of alveolar macrophages was increased at all three time-points upon LPS stimulation, while hypoxia did not affect apoptosis rate at early time-points. In neutrophils, apoptosis was decreased in an early phase of hypoxia at 4 h. However, enhanced expression of caspase-3 activity was seen at 8 and 24 h. In the presence of LPS a decreased apoptosis rate was observed at 8 h compared to controls, while it was increased at 24 h. Tracheobronchial as well as alveolar epithelial cells experienced an enhanced caspase-3 activity upon LPS stimulation with no change of apoptosis rate under hypoxia. While increased apoptosis rate is triggered through an intrinsic and extrinsic pathway in alveolar macrophages, intrinsic signalling is activated in tracheobronchial epithelial cells. The exact pathway pattern in neutrophils and alveolar epithelial cells could not be determined. These data clearly demonstrate that upon injury each cell type experiences its own apoptosis pattern. Further experiments need to be performed to determine the functional role of these apoptotic processes in acute lung injury.
细胞凋亡已被认为是急性肺损伤的潜在机制。为了评估这一过程的证据，我们在体外研究了低氧和内毒素刺激对呼吸区效应细胞（肺泡巨噬细胞、中性粒细胞）和靶细胞（气管支气管和肺泡上皮细胞）的影响，测定了凋亡率。细胞分别暴露于 5%的氧气或孵育脂多糖（LPS）4、8 和 24 小时，并测定了 caspase-3、-8 和 -9 的活性。LPS 刺激时，肺泡巨噬细胞的 caspase-3 在所有三个时间点均增加，而低氧在早期阶段并不影响凋亡率。在中性粒细胞中，低氧在 4 小时的早期阶段会减少细胞凋亡。然而，在 8 和 24 小时时观察到 caspase-3 活性的增强。在 LPS 存在的情况下，与对照组相比，8 小时的凋亡率降低，而 24 小时的凋亡率增加。气管支气管和肺泡上皮细胞在 LPS 刺激下 caspase-3 活性增强，而低氧时凋亡率没有变化。虽然肺泡巨噬细胞中通过内在和外在途径触发了凋亡率的增加，但在气管支气管上皮细胞中激活了内在信号。中性粒细胞和肺泡上皮细胞中的确切途径模式尚不清楚。这些数据清楚地表明，在损伤时，每种细胞类型都经历其自身的凋亡模式。需要进一步的实验来确定这些凋亡过程在急性肺损伤中的功能作用。
