Matsuse T, Fukuchi Y, Eto Y, Matsui H, Hosoi T, Oka T, Ohga E, Nagase T, Orimo H
Department of Geriatrics and Pathology, Faculty of Medicine, University of Tokyo, Japan.
Am J Respir Cell Mol Biol. 1995 Jul;13(1):17-24. doi: 10.1165/ajrcmb.13.1.7541220.
Activin A is a homodimeric protein structurally and functionally related to transforming growth factor beta (TGF-beta), and the expression of activin A is modulated by TGF-beta. Here, we demonstrate the expression of activin A in normal and bleomycin (BLM)-treated murine lungs. ICR mice were treated with BLM intraperitoneally for 10 days, whereas saline vehicle was injected into control mice. Intra-alveolar fibrotic changes were observed in the lung tissue obtained from the mice at day 14 after the final BLM administration. Immunohistochemical studies using a polyclonal antibody to activin A revealed the presence of activin A in the bronchiolar epithelium and smooth muscle cells of veins in both control and BLM-treated mice. In the BLM-treated mice at days 7 and 14, the marked infiltration of immunoreactive alveolar macrophages was observed in the area of fibrotic changes. Bioactivity of activin A measured by erythroid differentiation factor assay in the conditioned medium of alveolar macrophages obtained from BLM-treated mice at day 14 was significantly increased. These findings indicate that alveolar macrophages are a potent source of activin A after BLM treatment. The present study demonstrates for the first time the abundant expression of activin A in murine lung tissues after BLM administration, suggesting that activin A may play a role in the pathogenesis of BLM-induced pulmonary fibrosis.
激活素A是一种同二聚体蛋白，在结构和功能上与转化生长因子β（TGF-β）相关，且激活素A的表达受TGF-β调节。在此，我们证明了激活素A在正常和博来霉素（BLM）处理的小鼠肺组织中的表达。将ICR小鼠腹腔注射BLM 10天，而对照小鼠注射生理盐水。在最后一次给予BLM后第14天从小鼠获得的肺组织中观察到肺泡内纤维化改变。使用抗激活素A的多克隆抗体进行的免疫组织化学研究显示，在对照小鼠和BLM处理的小鼠的细支气管上皮和静脉平滑肌细胞中均存在激活素A。在BLM处理的小鼠第7天和第14天，在纤维化改变区域观察到免疫反应性肺泡巨噬细胞的明显浸润。在第14天从BLM处理的小鼠获得的肺泡巨噬细胞条件培养基中，通过红细胞分化因子测定法测得的激活素A的生物活性显著增加。这些发现表明，肺泡巨噬细胞是BLM处理后激活素A的重要来源。本研究首次证明了BLM给药后小鼠肺组织中激活素A的大量表达，提示激活素A可能在BLM诱导的肺纤维化发病机制中起作用。
