Departament of Pathology, Faculdade de Medicina da Universidade de São Paulo, Brasil.
Hum Pathol. 2010 Mar;41(3):385-91. doi: 10.1016/j.humpath.2009.08.019. Epub 2009 Dec 1.
Idiopathic pulmonary fibrosis is a distinctive, usually fatal, type of chronic fibrosing interstitial pneumonia of unknown cause that increases in prevalence with advanced age, characterized by failure of alveolar re-epithelization and progressive scar formation. Recently, limitation of the replicative capacity of tissues determined by telomerase/apoptosis balance has been implicated in pathogenesis of age-related diseases. In this study, we validated the importance of the expression of type 2 alveolar epithelial cells telomerase protein and studied the relationships between telomerase and apoptosis in early remodeling of usual interstitial pneumonia. We determined type 2 alveolar epithelial cells density, telomerase expression, and apoptosis in surgical lung biopsies from 24 patients with usual interstitial pneumonia, and in normal lung tissues from 18 subjects. We used immunohistochemistry, deoxynucleotidyl transferase method of end labeling, electron microscopy, and histomorphometry to evaluate the amount of type 2 alveolar epithelial cells staining for surfactant-A, telomerase, and in situ detection of apoptotic cells. Unaffected areas of usual interstitial pneumonia and normal lung tissue had similar densities of type 2 alveolar epithelial cells, but a significant minor subpopulation of type 2 alveolar epithelial cells was telomerase positive and a large population was telomerase negative. A significant inverse association was found between low type 2 alveolar epithelial cell telomerase expression and high apoptosis in unaffected areas of usual interstitial pneumonia. Although type 2 alveolar epithelial cell telomerase expression was higher than apoptosis in NLT group, no significant association was found between them. Electron microscopy confirmed epithelial apoptosis, alveolar collapse, and initial fibroplasia. We conclude that abnormal type 2 alveolar epithelial cells telomerase/apoptosis balance may reduce alveolar epithelial regenerative capacity, thus contributing to the early remodeling response in usual interstitial pneumonia.
特发性肺纤维化是一种独特的、通常致命的慢性纤维性间质性肺炎，其病因不明，随着年龄的增长而患病率增加，其特征是肺泡再上皮化失败和进行性瘢痕形成。最近，端粒酶/细胞凋亡平衡决定的组织复制能力的限制被认为与年龄相关疾病的发病机制有关。在这项研究中，我们验证了 2 型肺泡上皮细胞端粒酶蛋白表达的重要性，并研究了特发性肺纤维化早期重塑过程中端粒酶与细胞凋亡之间的关系。我们在 24 例特发性间质性肺炎患者的外科肺活检组织和 18 例正常肺组织中测定了 2 型肺泡上皮细胞密度、端粒酶表达和细胞凋亡。我们采用免疫组织化学、脱氧核苷酸转移酶末端标记法、电子显微镜和组织形态计量学方法评估表面活性物质 A、端粒酶和原位检测凋亡细胞的 2 型肺泡上皮细胞染色量。特发性间质性肺炎未受影响的区域和正常肺组织的 2 型肺泡上皮细胞密度相似，但存在一小部分 2 型肺泡上皮细胞端粒酶阳性，而大部分为端粒酶阴性。在特发性间质性肺炎未受影响的区域中，低 2 型肺泡上皮细胞端粒酶表达与高细胞凋亡呈显著负相关。尽管 2 型肺泡上皮细胞端粒酶表达高于 NLT 组的细胞凋亡，但两者之间无显著相关性。电子显微镜证实了上皮细胞凋亡、肺泡塌陷和早期纤维化。我们的结论是，异常的 2 型肺泡上皮细胞端粒酶/细胞凋亡平衡可能会降低肺泡上皮细胞的再生能力，从而导致特发性间质性肺炎的早期重塑反应。
