Subramaniam S, Whitsett J A, Hull W, Gairola C G
Tobacco & Health Research Institute, University of Kentucky, Lexington 40546-0236, USA.
Toxicol Appl Pharmacol. 1996 Oct;140(2):274-80. doi: 10.1006/taap.1996.0222.
Surfactant proteins (SP) play an important role in enhancing the surface properties of pulmonary surfactant and participate in host-defense mechanism(s) of the lung. Although it is known that cigarette smoking alters both pulmonary surfactant lipid composition and function, its effect on SPs is unknown. The present study was carried out to determine if chronic exposure to cigarette smoke alters pulmonary SPs, namely, SP-A and SP-B, in a rat model. Sprague-Dawley rats were exposed to cigarette smoke in a nose-only exposure system twice a day, every day for 70 weeks. At termination, bronchoalveolar lavage (BAL) fluid and the lung tissues were collected from room control, sham-treated (SH), and smoke-exposed (SM) animals for analyses. The total protein levels in the BAL fluid of SM rats tended to be higher but were not statistically different from those of the SH group. However, the albumin content of BAL fluid in SM rats, measured by quantitative immunoblotting, was significantly higher than in control groups. Compared to control groups, SP-A and SP-B levels in the BAL fluid of SM rats were significantly reduced by 25 and 50%, respectively, when expressed as units per microgram of BAL fluid protein. However, when calculated as total BAL fluid SP recovered per rat, only the SP-B levels of SM rats were significantly different from the control groups. Further analysis by ELISA confirmed the reduced levels of SP-B in SM rats. In contrast to BAL fluid, the lung tissue levels of SP and their respective mRNAs were not significantly different between the control and smoke-exposed groups. These results show a selective reduction in SP-B content on the bronchoalveolar surface following chronic exposure to cigarette smoke and suggest an inhibitory effect of cigarette smoke on surfactant secretory processes and/or a localized destruction of SPs on the bronchoalveolar surface.
表面活性物质蛋白(SP)在增强肺表面活性物质的表面特性方面发挥着重要作用,并参与肺的宿主防御机制。尽管已知吸烟会改变肺表面活性物质的脂质组成和功能,但其对表面活性物质蛋白的影响尚不清楚。本研究旨在确定在大鼠模型中,长期暴露于香烟烟雾是否会改变肺表面活性物质蛋白,即SP-A和SP-B。将Sprague-Dawley大鼠置于仅经鼻暴露系统中,每天暴露于香烟烟雾两次,持续70周。实验结束时,从室内对照、假处理(SH)和烟雾暴露(SM)的动物中收集支气管肺泡灌洗(BAL)液和肺组织进行分析。SM大鼠BAL液中的总蛋白水平有升高趋势,但与SH组相比无统计学差异。然而,通过定量免疫印迹法测定,SM大鼠BAL液中的白蛋白含量显著高于对照组。与对照组相比,以每微克BAL液蛋白中的单位数表示时,SM大鼠BAL液中SP-A和SP-B的水平分别显著降低了25%和50%。然而,当以每只大鼠回收的BAL液中SP的总量计算时,只有SM大鼠的SP-B水平与对照组有显著差异。通过酶联免疫吸附测定(ELISA)进一步分析证实了SM大鼠中SP-B水平降低。与BAL液相反,对照组和烟雾暴露组之间肺组织中SP及其各自mRNA的水平无显著差异。这些结果表明,长期暴露于香烟烟雾后,支气管肺泡表面的SP-B含量有选择性降低,并提示香烟烟雾对表面活性物质分泌过程有抑制作用和/或对支气管肺泡表面的表面活性物质有局部破坏作用。