McCrae K C, Rand T, Shaw R A, Mason C, Oulton M R, Hastings C, Cherlet T, Thliveris J A, Mantsch H H, MacDonald J, Scott J E
Departments of Oral Biology, Faculties of Dentistry and Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0W2.
Chem Phys Lipids. 2001 Mar;110(1):1-10. doi: 10.1016/s0009-3084(00)00199-7.
Lung cells are among the first tissues of the body to be exposed to air-borne environmental contaminants. Consequently the function of these cells may be altered before other cells are affected. As gas exchange takes place in the lungs, changes in cellular function may have serious implications for the processes of oxygen uptake and carbon dioxide elimination. In order for these processes to occur, the lung must maintain a high degree of expandability. This latter function is accomplished in part by the pulmonary surfactant which is synthesized and released by alveolar type II cells. Earlier studies have shown that exposure to gas phase materials such as smoke or organic solvents can alter the composition and function of the surfactant. The present study examines the ability of highly toxigenic mold spores to alter surfactant composition. Stachybotrys chartarum spores suspended in saline were instilled into mouse trachea as described earlier. After 24 h, the lungs were lavaged and the different processing stages of surfactant isolated by repeated centrifugation. Intracellular surfactant was isolated from the homogenized lung tissue by centrifugation on a discontinuous sucrose gradient. Samples were extracted into chloroform-methanol, dried and analyzed by Fourier-Transform infrared spectroscopy (FTIR). Exposure to S. chartarum induced an overall reduction of phospholipid among the three surfactant subfractions. The intermediate and spent surfactant fractions in particular were reduced to about half of the values observed in the saline-treated group. The relative distribution of phospholipid was also altered by spore exposure. Within the intracellular surfactant pool, higher levels of phospholipid were detected after spore exposure. In addition, changes were observed in the nature of the phospholipids. In particular strong intramolecular hydrogen bonding, together with other changes, suggested that spore exposure was associated with absence of an acyl chain esterified on the glycerol backbone, resulting in elevated levels of lysophospholipid in the samples. This study shows that mold spores and their products induce changes in regulation of both secretion and synthesis of surfactant, as well as alterations in the pattern of phospholipid targeting to the pulmonary surfactant pools.
肺细胞是人体最早接触空气传播环境污染物的组织之一。因此，这些细胞的功能可能在其他细胞受到影响之前就发生改变。由于气体交换在肺部进行，细胞功能的变化可能对氧气摄取和二氧化碳排出过程产生严重影响。为了使这些过程发生，肺必须保持高度的可扩展性。后一项功能部分由肺泡II型细胞合成和释放的肺表面活性物质来完成。早期研究表明，接触烟雾或有机溶剂等气相物质会改变表面活性物质的组成和功能。本研究考察了高毒性霉菌孢子改变表面活性物质组成的能力。如前所述，将悬浮在盐水中的链格孢霉菌孢子注入小鼠气管。24小时后，冲洗肺部，并通过反复离心分离表面活性物质的不同加工阶段。通过在不连续蔗糖梯度上离心，从匀浆的肺组织中分离细胞内表面活性物质。样品用氯仿 - 甲醇萃取、干燥，并用傅里叶变换红外光谱（FTIR）分析。接触链格孢霉菌导致三种表面活性物质亚组分中的磷脂总体减少。特别是中间和消耗的表面活性物质组分减少到盐水处理组观察值的约一半。孢子暴露也改变了磷脂的相对分布。在细胞内表面活性物质池中，孢子暴露后检测到较高水平的磷脂。此外，观察到磷脂性质的变化。特别是强烈的分子内氢键以及其他变化表明，孢子暴露与甘油主链上未酯化的酰基链缺失有关，导致样品中溶血磷脂水平升高。这项研究表明，霉菌孢子及其产物会诱导表面活性物质分泌和合成调节的变化，以及磷脂靶向肺表面活性物质池模式的改变。
