State of the art. Cellular and molecular mechanisms of alveolar destruction in emphysema: an evolutionary perspective.
State of the art. Cellular and molecular mechanisms of alveolar destruction in emphysema: an evolutionary perspective.
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DOI：
10.1513/pats.200603-054ms
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发表时间：
2006-08-01
期刊：
影响因子：
--
通讯作者：
Petrache, Irina
中科院分区：
文献类型：
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作者：
Tuder, Rubin M;Yoshida, Toshinori;Petrache, Irina
肺气肿由一种独特的肺泡破坏模式组成，导致气腔明显扩大，肺泡毛细血管交换面积减少。肺气肿发病机制的经典概念依赖于炎症和蛋白酶/抗蛋白酶失衡所设定的范式。我们在此提出，香烟烟雾构成一种环境危害，通过细胞凋亡、氧化应激和蛋白酶/抗蛋白酶失衡的相互作用导致肺泡破坏。我们将机体衰老、器官结构维护和长期吸入香烟烟雾造成的损害进行类比。环境危害与生物体或特定器官抵御这些危害的努力之间的随机相互作用导致细胞损伤的积累和衰老特征。损伤的倍增会导致炎症。我们强调了解肺泡细胞在稳态和肺泡破坏中相互作用的生物学的重要性，以及与衰老和应激反应相关的新过程的潜在作用。肺气肿的进化视角结合了与衰老相关的机制，可能会在慢性阻塞性肺病的理解和治疗靶向方面带来重要进展。
Emphysema consists of a unique pattern of alveolar destruction, resulting in marked airspace enlargement with reduction of alveolar capillary exchange area. Classical concepts of the pathogenesis of emphysema have relied on the paradigm set by the inflammation and protease/antiprotease imbalance. We propose herein that cigarette smoke constitutes an environmental hazard that causes alveolar destruction by the interaction of apoptosis, oxidative stress, and protease/antiprotease imbalance. We draw a parallel between organismal aging, organ structural maintenance, and the damage resulting from chronic cigarette smoke inhalation. The stochastic interaction between environmental hazards and the effort of an organism or a particular organ to fend off these hazards results in the accumulation of cellular damage and features characteristic of aging. Inflammation follows as the result of the multiplication of injuries. We highlight the importance of understanding the biology of the interaction of alveolar cells in homeostasis and in alveolar destruction, and the potential role of novel processes related to senescence and stress response. An evolutionary perspective of emphysema that incorporates mechanisms related to aging may lead to important advances in the understanding and therapeutic targeting of chronic obstructive pulmonary disease.