Guinee D, Fleming M, Hayashi T, Woodward M, Zhang J, Walls J, Koss M, Ferrans V, Travis W
Department of Pathology, University of Utah, Salt Lake City 84132, USA.
Am J Pathol. 1996 Aug;149(2):531-8.
Little is known about alterations in cell cycle regulatory proteins such as p53 and WAF1 in diffuse alveolar damage (DAD). We hypothesized that up-regulation of p53 and WAF1 in type II pneumocytes in DAD is associated with underlying DNA damage and apoptosis. Twenty cases of DAD and twenty control specimens of lung adjacent to resected tumors were studied. Immunohistochemical stains with antibodies recognizing p53 and WAF1 were performed, and apoptosis was assessed in sixteen cases by the nick end-labeling method. We identified p53 expression and apoptosis in all cases of DAD but not in any of the control lungs. We detected WAF1 expression in nineteen of twenty cases of DAD and in sixteen of twenty control lungs. In general, the distribution and intensity of WAF1 staining were greater in DAD than in control lungs. Staining for both p53 and WAF1 and labeling of apoptotic cells in DAD were usually focal ( < 10% of cells) and predominantly localized in type II pneumocytes. We conclude that increased p53 and WAF1 expression in DAD reflects normal physiological up-regulation in response to cellular and DNA damage and is associated with apoptosis of type II pneumocytes. p53-dependent apoptosis may contribute to the pathogenesis of this disease.
关于弥漫性肺泡损伤（DAD）中细胞周期调节蛋白如p53和WAF1的改变，目前所知甚少。我们推测，DAD中II型肺泡上皮细胞中p53和WAF1的上调与潜在的DNA损伤和细胞凋亡有关。研究了20例DAD病例和20例与切除肿瘤相邻的肺对照标本。用识别p53和WAF1的抗体进行免疫组织化学染色，并通过缺口末端标记法对16例病例的细胞凋亡进行评估。我们在所有DAD病例中均发现了p53表达和细胞凋亡，但在任何对照肺组织中均未发现。我们在20例DAD病例中的19例以及20例对照肺组织中的16例中检测到了WAF1表达。总体而言，DAD中WAF1染色的分布和强度高于对照肺组织。DAD中p53和WAF1的染色以及凋亡细胞的标记通常呈局灶性（<10%的细胞），且主要定位于II型肺泡上皮细胞。我们得出结论，DAD中p53和WAF1表达的增加反映了对细胞和DNA损伤的正常生理上调，并且与II型肺泡上皮细胞的凋亡有关。p53依赖性细胞凋亡可能参与了该疾病的发病机制。
