Iwashita T, Kadota J, Naito S, Kaida H, Ishimatsu Y, Miyazaki M, Ozono Y, Kohno S
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Hum Pathol. 2000 Dec;31(12):1498-505. doi: 10.1053/hupa.2000.20378.
The most common pathologic form of idiopathic pulmonary fibrosis is usual interstitial pneumonia, which is characterized by patchy fibrotic areas, marked increase in the number of fibroblasts and type II pneumocytes, and excessive deposition of extracellular matrix proteins, especially collagen. Heat shock protein 47 is a collagen-binding stress protein and has a specific role in intracellular processing of procollagen molecules as a collagen-specific molecular chaperone. However, its role in the causation of fibrosis in usual interstitial pneumonia is unknown. In this study, we examined the expression of heat shock protein 47 and type I procollagen in 12 patients with usual interstitial pneumonia by immunohistochemistry on sequential sections. Heat shock protein 47 was localized predominantly in alpha-smooth muscle actin-positive myofibroblasts and surfactant protein-A-positive type II pneumocytes in active fibrotic areas of usual interstitial pneumonia. Type I procollagen was also expressed in those cells. In contrast, heat shock protein 47 and type I procollagen were weakly or not at all expressed in myofibroblasts and type II pneumocytes in bronchiolitis obliterans organizing pneumonia and normal lung tissue samples obtained from excised lung cancer tissues. The numbers of heat shock protein 47- and type I procollagen-positive cells to type II pneumocytes or myofibroblasts were significantly higher in usual interstitial pneumonia than in bronchiolitis obliterans organizing pneumonia and normal lung tissue specimens. Our results suggest that myofibroblasts and type II pneumocytes play an important role in the progression of fibrosis through the induction of heat shock protein 47, which regulates the synthesis/assembly of type I procollagen in usual interstitial pneumonia. HUM PATHOL 31:1498-1505.
特发性肺纤维化最常见的病理形式是普通型间质性肺炎，其特征为斑片状纤维化区域、成纤维细胞和II型肺细胞数量显著增加，以及细胞外基质蛋白尤其是胶原蛋白的过度沉积。热休克蛋白47是一种胶原结合应激蛋白，作为一种胶原特异性分子伴侣，在细胞内原胶原分子的加工过程中起特定作用。然而，其在普通型间质性肺炎纤维化病因中的作用尚不清楚。在本研究中，我们通过连续切片免疫组化检查了12例普通型间质性肺炎患者热休克蛋白47和I型前胶原的表达。热休克蛋白47主要定位于普通型间质性肺炎活跃纤维化区域的α平滑肌肌动蛋白阳性肌成纤维细胞和表面活性蛋白A阳性II型肺细胞中。I型前胶原也在这些细胞中表达。相比之下，在闭塞性细支气管炎机化性肺炎和从切除的肺癌组织获得的正常肺组织样本的肌成纤维细胞和II型肺细胞中，热休克蛋白47和I型前胶原表达微弱或根本不表达。普通型间质性肺炎中热休克蛋白47和I型前胶原阳性细胞与II型肺细胞或肌成纤维细胞的数量显著高于闭塞性细支气管炎机化性肺炎和正常肺组织标本。我们的结果表明，肌成纤维细胞和II型肺细胞通过诱导热休克蛋白47在纤维化进展中起重要作用，热休克蛋白47在普通型间质性肺炎中调节I型前胶原的合成/组装。《人类病理学》31:1498 - 1505。
