Cantin A M, Fells G A, Hubbard R C, Crystal R G
Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Clin Invest. 1990 Sep;86(3):962-71. doi: 10.1172/JCI114798.
We hypothesized that the alveolar structures may contain extracellular macromolecules with antioxidant properties to defend against oxidants. To evaluate this 51Cr-labeled human lung fibroblasts (HFL-1) and cat lung epithelial cells (AKD) were exposed to a H2O2-generating system and alveolar epithelial lining fluid (ELF) from healthy nonsmokers was tested for its ability to protect the lung cells from H2O2-mediated injury. The ELF provided marked antioxidant protection, with most from a H2O-soluble fraction in the 100-300-kD range. Plasma proteins with anti-H2O2 properties were in insufficient concentrations to provide the antioxidant protection observed. However, catalase, a normal intracellular antioxidant, was present in sufficient concentration to account for most of the observed anti-H2O2 properties of ELF. Depletion of ELF with an anticatalase antibody abolished the anti-H2O2 macromolecular defenses of ELF. Since catalase is not normally released by cells, a likely explanation for its presence in high concentrations in normal ELF is that it is released by lung inflammatory and parenchymal cells onto the epithelial surface of the lower respiratory tract during their normal turnover and collects there due to the slow turnover of ELF. It is likely that catalase in the ELF of normal individuals plays a role in protecting lung parenchymal cells against oxidants present in the extracellular milieu.
我们推测肺泡结构可能含有具有抗氧化特性的细胞外大分子,以抵御氧化剂。为了评估这一点,将51Cr标记的人肺成纤维细胞(HFL-1)和猫肺上皮细胞(AKD)暴露于一个产生H2O2的系统中,并检测来自健康非吸烟者的肺泡上皮衬液(ELF)保护肺细胞免受H2O2介导损伤的能力。ELF提供了显著的抗氧化保护,大部分来自100-300-kD范围内的水溶性部分。具有抗H2O2特性的血浆蛋白浓度不足以提供所观察到的抗氧化保护。然而,过氧化氢酶,一种正常的细胞内抗氧化剂,其浓度足以解释ELF所观察到的大部分抗H2O2特性。用抗过氧化氢酶抗体耗尽ELF消除了ELF的抗H2O2大分子防御。由于过氧化氢酶通常不会由细胞释放,其在正常ELF中高浓度存在的一个可能解释是,它是由肺部炎症细胞和实质细胞在其正常更新过程中释放到下呼吸道上皮表面,并由于ELF的缓慢更新而在那里聚集。正常个体ELF中的过氧化氢酶可能在保护肺实质细胞免受细胞外环境中存在的氧化剂的影响方面发挥作用。