INCREASED PRODUCTION AND IMMUNOHISTOCHEMICAL LOCALIZATION OF TRANSFORMING GROWTH-FACTOR-BETA IN IDIOPATHIC PULMONARY FIBROSIS
INCREASED PRODUCTION AND IMMUNOHISTOCHEMICAL LOCALIZATION OF TRANSFORMING GROWTH-FACTOR-BETA IN IDIOPATHIC PULMONARY FIBROSIS
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DOI：
10.1165/ajrcmb/5.2.155
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发表时间：
1991-08-01
影响因子：
6.4
通讯作者：
GREENBERG, AH
中科院分区：
文献类型：
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作者：
KHALIL, N;OCONNOR, RN;GREENBERG, AH
转化生长因子-β（TGF-β）可以调节细胞生长和分化以及细胞外基质蛋白的产生。 TGF-β的产生增加与人类和啮齿动物的慢性炎症和纤维化疾病有关。 使用免疫组织化学染色，我们检查了晚期特发性肺纤维化（IPF）患者的肺切片，IPF是一种以慢性炎症和纤维化为特征的疾病，与非特异性炎症和无炎症或纤维化的患者相比，其上皮细胞和巨噬细胞中TGF-β的产生显著且一致地增加。 在晚期IPF患者中，在细支气管上皮细胞中显著观察到抗LC（1-30）TGF-β抗体的细胞内染色。 此外，蜂窝状囊肿的上皮细胞和增生的II型肺细胞染色强烈。 与细胞外TGF-β反应的抗CC（1-30）TGF-β抗体定位于细支气管固有层和致密纤维结缔组织沉积区域的蜂窝囊肿上皮下区域。 在晚期IPF中，上皮下TGF-β与细胞内形式密切相关，表明TGF-β主要由上皮细胞产生和分泌。 由于TGF-β对细胞外基质形成和上皮细胞分化的众所周知的作用，晚期IPF中TGF-β的产生增加可能是这种疾病中观察到的肺纤维化和再生反应的致病性。
Transforming growth factor-beta (TGF-beta) can regulate cell growth and differentiation as well as production of extracellular matrix proteins. Elevated production of TGF-beta has been associated with human and rodent chronic inflammatory and fibrotic diseases. Using immunohistochemical staining, we have examined lung sections of patients with advanced idiopathic pulmonary fibrosis (IPF), a disease characterized by chronic inflammation and fibrosis and demonstrated a marked and consistent increase in TGF-beta production in epithelial cells and macrophages when compared to patients with nonspecific inflammation and those with no inflammation or fibrosis. In patients with advanced IPF, intracellular staining with anti-LC (1-30) TGF-beta antibody was seen prominently in bronchiolar epithelial cells. In addition, epithelial cells of honeycomb cysts and hyperplastic type II pneumocytes stained intensely. Anti-CC (1-30) TGF-beta antibody, which reacts with extracellular TGF-beta, was localized in the lamina propria of bronchioles and in subepithelial regions of honeycomb cysts in areas of dense fibroconnective tissue deposition. The close association of subepithelial TGF-beta to the intracellular form in advanced IPF suggests that TGF-beta was produced and secreted primarily by epithelial cells. Because of the well-known effects of TGF-beta on extracellular matrix formation and on epithelial cell differentiation, the increased production of TGF-beta in advanced IPF may be pathogenic to the pulmonary fibrotic and regenerative responses seen in this disease.