First Department of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, Japan.
Proc Am Thorac Soc. 2009 Dec 1;6(7):596-601. doi: 10.1513/pats.200904-017RM.
We report herein that pulmonary emphysematous lesions appear to be a dynamic phenomenon that involves not only the gradual loss of alveolar structure but also apoptosis, cellular proliferation, and cellular senescence. Cellular proliferation compensates for increased alveolar cell apoptosis in patients with chronic obstructive pulmonary disease (COPD). However, smoking, age, and the increased cell cycle turnover that compensates for apoptosis accelerate alveolar cell senescence, thereby halting cellular proliferation and tipping the balance toward apoptosis, which, in turn, promotes the formation of emphysematous lesions. As a result, alveolar cells disappear and the emphysematous lesions progress. At the same time, cellular senescence is believed to induce inflammation. More specifically, senescent alveolar cells induce inflammation by producing various inflammatory cytokines in tissue. Lymphocytes and Clara cells may also age more rapidly in the lungs of patients with COPD. Lymphocyte senescence may induce an autoimmune reaction and increase susceptibility to infection, and Clara cell senescence may impair airway regeneration as well as sustain airway inflammation. Thus, cellular senescence may be involved in arrested tissue repair, chronic inflammation, and increased susceptibility to infection, which are the typical features of COPD.
我们在此报告，肺气肿病变似乎是一种动态现象，不仅涉及肺泡结构的逐渐丧失，还涉及细胞凋亡、细胞增殖和细胞衰老。在慢性阻塞性肺疾病（COPD）患者中，细胞增殖可代偿性地增加肺泡细胞凋亡。然而，吸烟、年龄以及代偿性凋亡的细胞周期周转率增加会加速肺泡细胞衰老，从而停止细胞增殖，使平衡向凋亡倾斜，进而促进肺气肿病变的形成。结果，肺泡细胞消失，肺气肿病变进展。同时，细胞衰老被认为会引发炎症。更具体地说，衰老的肺泡细胞通过在组织中产生各种炎症细胞因子引发炎症。COPD 患者的肺部中的淋巴细胞和克拉拉细胞也可能更快地衰老。淋巴细胞衰老可能会引起自身免疫反应，增加感染易感性，而克拉拉细胞衰老可能会损害气道再生并维持气道炎症。因此，细胞衰老可能与组织修复停滞、慢性炎症和感染易感性增加有关，这些都是 COPD 的典型特征。
