Yamashita Masahiro, Yamauchi Kohei, Chiba Ryoji, Iwama Noriyuki, Date Fumiko, Shibata Naoko, Kumagai Hiroyuki, Risteli Juha, Sato Shinobu, Takahashi Tohru, Ono Masao
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
Hum Pathol. 2009 Sep;40(9):1278-87. doi: 10.1016/j.humpath.2009.01.014. Epub 2009 Apr 22.
There is limited information regarding the process of tissue remodeling in fibroblastic foci associated with idiopathic pulmonary fibrosis. The aim of this study was to identify the different pathologic stages of tissue remodeling in fibroblastic foci based on the histopathologic differences in the glycosaminoglycan distribution and collagen deposition. In addition, we also aimed at clarifying the stage-specific characteristics by taking into consideration the expression pattern of matrix metalloproteinase and angiogenesis. Lung biopsies of 16 patients with idiopathic pulmonary fibrosis were used. The presence of glycosaminoglycans was detected by Alcian blue staining, and type I collagen was detected by immunohistochemical analysis with a primary antibody specific to the cross-linked carboxyterminal telopeptide of type I collagen. The fibroblastic foci characterized by the expression intensity of Alcian blue and telopeptide of type I collagen were divided into 3 groups, namely, Alcian blue(+)telopeptide of type I collagen(weak), Alcian blue(+)telopeptide of type I collagen(+), and Alcian blue(weak)telopeptide of type I collagen(+); consequently, 3 new stages were defined--stages I, II, and III, respectively. A significant inverse correlation was observed between the area densities of Alcian blue(+) and telopeptide of type I collagen(+) in fibroblastic foci. Stage I was characterized by the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloprotease-2 in fibroblasts and the overlying epithelium of fibroblastic foci, and also the absence of capillary angiogenesis. In contrast, the expression of these proteins was attenuated in stage III, except for that of matrix metalloproteinase-2 in fibroblasts. In stages II and III, capillary angiogenesis was observed. Lymphangiogenesis was undetected in all the 3 stages. Thus, pathologic staging helps understand the roles of the factors involved in tissue remodeling in idiopathic pulmonary fibrosis.
关于与特发性肺纤维化相关的成纤维细胞灶中组织重塑过程的信息有限。本研究的目的是基于糖胺聚糖分布和胶原蛋白沉积的组织病理学差异，确定成纤维细胞灶中组织重塑的不同病理阶段。此外，我们还旨在通过考虑基质金属蛋白酶的表达模式和血管生成来阐明阶段特异性特征。使用了16例特发性肺纤维化患者的肺活检标本。通过阿尔辛蓝染色检测糖胺聚糖的存在，并用针对I型胶原蛋白交联羧基末端肽的一抗进行免疫组织化学分析检测I型胶原蛋白。根据阿尔辛蓝和I型胶原蛋白肽的表达强度，将成纤维细胞灶分为3组，即阿尔辛蓝（+）I型胶原蛋白肽（弱）、阿尔辛蓝（+）I型胶原蛋白肽（+）和阿尔辛蓝（弱）I型胶原蛋白肽（+）；因此，分别定义了3个新的阶段——I期、II期和III期。在成纤维细胞灶中，观察到阿尔辛蓝（+）和I型胶原蛋白肽（+）的面积密度之间存在显著的负相关。I期的特征是成纤维细胞和成纤维细胞灶上方上皮中基质金属蛋白酶-2和基质金属蛋白酶组织抑制剂-2的表达，以及不存在毛细血管血管生成。相比之下，除了成纤维细胞中基质金属蛋白酶-2的表达外，这些蛋白在III期的表达减弱。在II期和III期观察到毛细血管血管生成。在所有3个阶段均未检测到淋巴管生成。因此，病理分期有助于了解特发性肺纤维化中参与组织重塑的因素的作用。
