Endothelial Alpha-1-Antitrypsin Attenuates Cigarette Smoke Induced Apoptosis In Vitro
Endothelial Alpha-1-Antitrypsin Attenuates Cigarette Smoke Induced Apoptosis In Vitro
复制标题
DOI：
10.1080/15412550802092936
复制
发表时间：
2008-06-01
影响因子：
2.2
通讯作者：
Zhang, Jianliang
中科院分区：
文献类型：
--
作者：
Aldonyte, Ruta;Hutchinson, Edgar Tarun;Zhang, Jianliang
背景：抗蛋白酶α-1抗胰蛋白酶(AAT)缺乏和香烟烟雾(CS)暴露导致早发性肺气肿的发生。CS诱导的肺泡细胞包括内皮细胞的凋亡在肺损伤中起重要作用。AAT缺乏也与肺组织破坏增加有关。我们假设AAT保护肺泡免受有害环境刺激，如CS诱导的细胞凋亡。方法：将培养的猪肺动脉内皮细胞(PAEC)暴露于含或不含AAT(20mM)的CS中。共聚焦显微镜观察AAT内化和细胞凋亡标志物的变化。流式细胞术平行进行，以定量AAT负载和凋亡细胞的数量。结果：我们发现外源性AAT在PAEC中积聚，并保护细胞免受CS诱导的细胞凋亡。与未经AAT处理的CS暴露的细胞相比，AAT负载的CS暴露的细胞显示其胞浆中伴侣HSP-70的数量增加，而细胞核中的凋亡诱导因子减少。结论：AAT通过两种机制被内皮细胞摄取，细胞内AAT对CS诱导的内皮细胞凋亡可能具有保护作用。这可能会为内皮蛇毒作为能够保护血管系统免受环境有害物质伤害的试剂领域提供新的见解。
Background: Deficiency of the antiprotease alpha-1-antitrypsin (AAT) and exposure to cigarette smoke (CS) contribute to the development of early onset emphysema. CS-induced apoptosis of alveolar cells including endothelial cells plays critical role in the lung destruction. AAT deficiency is associated with increased lung tissue destruction as well. We hypothesize that AAT protects lung alveoli from noxious environmental stimuli such as CS-induced apoptosis. Methods: Porcine pulmonary artery endothelial cells (PAEC) were exposed to CS in the presence or absence of AAT (20 mu M). AAT internalization and markers for apoptosis were assessed by confocal microscopy. Flow cytometry was performed in parallel to quantify the number of AAT-loaded and apoptotic cells. Results: We demonstrated that exogenous AAT accumulated in PAEC and protected cells from CS-induced apoptosis. AAT-loaded CS-exposed cells exhibited increased amounts of chaperone HSP-70 in their cytosol and less apoptosis inducing factor in their nuclei compared to AAT-untreated, CS-exposed cells. Conclusions: Our results suggest that AAT is taken up by endothelial cells via two mechanisms and that intracellular AAT may have a protective role in CS-induced endothelial apoptosis. This may open new insights into the field of endothelial serpins as agents capable of protecting the vasculature from environment-derived noxious substances.