Correlation of lung surface area to apoptosis and proliferation in human emphysema
Correlation of lung surface area to apoptosis and proliferation in human emphysema
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DOI：
10.1183/09031936.05.00023704
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发表时间：
2005-02-01
影响因子：
24.3
通讯作者：
D'Armiento, JM
中科院分区：
文献类型：
--
作者：
Imai, K;Mercer, BA;D'Armiento, JM
肺气肿与基质蛋白和蛋白酶活性的改变有关。这些变化可能与程序性细胞死亡的细胞凋亡，潜在地影响肺结构和肺functions.To评估肺气肿，肺组织中的细胞凋亡进行了分析，从10个肺气肿患者和6个人没有肺气肿（正常）。形态学分析显示，肺气肿肺中的肺泡细胞具有细胞凋亡特征的卷曲核。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）和凝胶电泳检测DNA片段化。TUNEL法显示肺气肿肺组织细胞凋亡明显高于正常肺组织。检测肺气肿肺组织中凋亡标志物caspase-3活性、多聚腺苷二磷酸核糖聚合酶蛋白水解片段、Bax和Bad。线性回归显示细胞凋亡与表面积呈负相关。肺气肿肺表现出较低的表面积和细胞增殖增加。细胞凋亡和增殖之间没有相关性，这表明，虽然这两个事件增加在肺气肿，他们不是在平衡，可能有助于减少肺表面积。总之，与肺气肿实质损伤相关的细胞为基础的机制，包括增加细胞凋亡和细胞增殖。细胞凋亡与肺空间扩大相关，支持肺气肿进行性的流行病学证据。这些数据扩展了对肺气肿发病过程中肺内细胞动力学和结构变化的理解。
Pulmonary emphysema is associated with alterations in matrix proteins and protease activity. These alterations may be linked to programmed cell death by apoptosis, potentially influencing lung architecture and lung function.To evaluate apoptosis in emphysema, lung tissue was analysed from 10 emphysema patients and six individuals without emphysema (normal). Morphological analysis revealed alveolar cells in emphysematous lungs with convoluted nuclei characteristic of apoptosis. DNA fragmentation was detected using terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL) and gel electrophoresis. TUNEL revealed higher apoptosis in emphysematous than normal lungs. Markers of apoptosis, including active caspase-3, proteolytic fragment of poly (ADP-ribose) polymerase, Bax and Bad, were detected in emphysematous lungs. Linear regression showed that apoptosis was inversely correlated with surface area. Emphysematous lungs demonstrated lower surface areas and increased cell proliferation. There was no correlation between apoptosis and proliferation, suggesting that, although both events increase during emphysema, they are not in equilibrium, potentially contributing to reduced lung surface area.In summary, cell-based mechanisms associated with emphysematous parenchymal damage include increased apoptosis and cell proliferation. Apoptosis correlated with airspace enlargement, supporting epidemiological evidence of the progressive nature of emphysema. These data extend the understanding of cell dynamics and structural changes within the lung during emphysema pathogenesis.