Kumar R K, O'Grady R, Maronese S E, Wilson M R
School of Pathology, University of New South Wales, Sydney, Australia.
Int J Exp Pathol. 1996 Jun;77(3):99-107. doi: 10.1046/j.1365-2613.1996.586969.x.
We have investigated whether enhanced secretion of transforming growth factor-beta (TGF-beta) by distal respiratory epithelial cells was associated with the development of bleomycin-induced pulmonary fibrosis. Type 2 pneumocyte-enriched preparations of bronchioloalveolar epithelial cells from normal mouse lung tissue released latent TGF-beta when cultured in serum-free medium. TGF-beta in culture supernatants could be detected using a sensitive enzyme immunoassay which employed enzyme complex amplification as a reporter system, as well as by a radiolabelled receptor competition assay. Exposure to bleomycin and other potentially fibrogenic stimuli in vitro did not stimulate production of TGF-beta by the epithelial cells but release was enhanced by treatment of the cells with interferon-gamma. Type 2 pneumocyte-enriched cell preparations obtained following induction of a pulmonary inflammatory response by administration of intratracheal bleomycin to susceptible C57BL/6 mice did not demonstrate increased release of TGF-beta in culture. However, the concentration of TGF-beta in bronchoalveolar lavage (BAL) fluids was significantly elevated compared to controls at 1 and 2 weeks after bleomycin-induced injury in these mice. No such increase was detected in BAL fluids from BALB/c mice, which are resistant to the effects of bleomycin. These results provide no support for a pathogenetic role of alveolar epithelial cell-derived TGF-beta in bleomycin-induced pulmonary fibrosis. Nevertheless, elevated levels of TGF-beta in BAL fluids may provide a marker of the progression of pulmonary injury to fibrosis.
我们研究了远端呼吸道上皮细胞分泌转化生长因子-β（TGF-β）增加是否与博来霉素诱导的肺纤维化的发生有关。来自正常小鼠肺组织的细支气管肺泡上皮细胞中富含Ⅱ型肺细胞的制剂在无血清培养基中培养时会释放潜伏性TGF-β。培养上清液中的TGF-β可以使用一种敏感的酶免疫测定法检测，该方法采用酶复合物扩增作为报告系统，也可以通过放射性标记的受体竞争测定法检测。体外暴露于博来霉素和其他潜在的致纤维化刺激物不会刺激上皮细胞产生TGF-β，但用干扰素-γ处理细胞会增强其释放。对易感的C57BL/6小鼠气管内给予博来霉素诱导肺部炎症反应后获得的富含Ⅱ型肺细胞的细胞制剂在培养中未显示TGF-β释放增加。然而，在这些小鼠博来霉素诱导损伤后1周和2周时，支气管肺泡灌洗（BAL）液中TGF-β的浓度与对照组相比显著升高。在对博来霉素作用有抗性的BALB/c小鼠的BAL液中未检测到这种增加。这些结果不支持肺泡上皮细胞来源的TGF-β在博来霉素诱导的肺纤维化中的致病作用。然而，BAL液中TGF-β水平的升高可能是肺损伤进展为纤维化的一个标志物。
