Iyonaga K, Miyajima M, Suga M, Saita N, Ando M
First Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
J Pathol. 1997 Jun;182(2):217-24. doi: 10.1002/(SICI)1096-9896(199706)182:2<217::AID-PATH833>3.0.CO;2-A.
It is generally recognized that epithelial cytokeratins (CKs) are expressed in tissue-specific patterns and reflect differentiation, functional specialization, and pathological alterations of the cells. Differential epithelial cell types can thus be distinguished from each other by their selective expression of particular sets of CKs. To determine the characteristics of metaplastic and hyperplastic changes of alveolar-lining epithelial cells in the lungs of idiopathic pulmonary fibrosis (IPF), the expression of individual CKs was studied immunohistochemically using monospecific anti-CK monoclonal antibodies (anti-CKs 7, 8, 10, 13, 14, 16, 17, 18, 19). Biopsy specimens from 17 patients with IPF and normal lung tissues (NL) from seven patients with lung cancer were studied. In the IPF specimens, several kinds of altered epithelial cells were observed, which showed characteristic changes in CK expression compared with NL, especially CKs 8, 14, and 17. Hyperplastic type II cells expressed increased CKs 7, 8, and 19, but not CK 17; flattened or stratified squamous metaplastic cells expressed increased CKs 17 and 14, co-expressed with CKs 7, 8, and 19; bronchiolar metaplastic cells expressed increased CKs 7, 8, and 19, co-expressed with CKs 14 and 17; cuboidal metaplastic cells expressed increased CKs 7, 8, 17, and 19. The quantification of individual CKs in the tissues by enzyme-linked immunosorbent assay revealed increased expression of CKs 8, 14, and 17 in IPF lung tissues compared with NL. These results were consistent with the immunohistochemical observations. The hyperplastic and bronchiolar metaplastic phenotypes were characterized by their increased expression of simple CKs without CK alteration. The squamous metaplastic phenotype showed CK alterations, with the appearance of CKs 17 and 14. Epithelial cells are thus altered not only in shape, but possibly also in differentiation and function, with potential implications for the pathogenesis of IPF.
一般认为，上皮细胞角蛋白（CKs）以组织特异性模式表达，反映细胞的分化、功能特化及病理改变。不同的上皮细胞类型可通过其对特定CKs组合的选择性表达而相互区分。为确定特发性肺纤维化（IPF）患者肺组织中肺泡内衬上皮细胞化生和增生变化的特征，使用单特异性抗CK单克隆抗体（抗CKs 7、8、10、13、14、16、17、18、19）通过免疫组织化学方法研究了单个CKs的表达。研究了17例IPF患者的活检标本以及7例肺癌患者的正常肺组织（NL）。在IPF标本中，观察到几种改变的上皮细胞，与NL相比，其CK表达呈现特征性变化，尤其是CKs 8、14和17。增生的II型细胞CKs 7、8和19表达增加，但CK 17不增加；扁平或分层的鳞状化生细胞CKs 17和14表达增加，与CKs 7、8和19共表达；细支气管化生细胞CKs 7、8和19表达增加，与CKs 14和17共表达；立方形化生细胞CKs 7、8、17和19表达增加。通过酶联免疫吸附测定对组织中单个CKs进行定量分析显示，与NL相比，IPF肺组织中CKs 8、14和17表达增加。这些结果与免疫组织化学观察结果一致。增生和细支气管化生表型的特征是简单CKs表达增加而无CK改变。鳞状化生表型显示CK改变，出现了CKs 17和14。因此，上皮细胞不仅在形态上发生改变，而且在分化和功能上可能也发生改变，这对IPF的发病机制具有潜在影响。
