Cantin A M, North S L, Fells G A, Hubbard R C, Crystal R G
J Clin Invest. 1987 Jun;79(6):1665-73. doi: 10.1172/JCI113005.
Lung inflammatory cells of patients with idiopathic pulmonary fibrosis (IPF) were evaluated for their ability to injure 51Cr-labeled AKD alveolar epithelial cells in the presence and absence of IPF alveolar epithelial lining fluid (ELF). The IPF cells were spontaneously releasing exaggerated amounts of superoxide (O.2) and hydrogen peroxide (H2O2) compared with normal (P less than 0.02). Cytotoxicity of the AKD cells was markedly increased when the IPF inflammatory cells were incubated with autologous ELF (P less than 0.02). The majority of IPF patients had ELF myeloperoxidase levels above normal (P less than 0.002). Incubation of IPF ELF with AKD cells in the presence of H2O2 caused increased cellular injury (P less than 0.01 compared with control), which was suppressed by methionine, a myeloperoxidase system scavenger. IPF patients with high concentrations of ELF myeloperoxidase deteriorated more rapidly than those with low ELF myeloperoxidase (P less than 0.05). Thus, IPF is characterized by an increased spontaneous production of oxidants by lung inflammatory cells, the presence of high concentrations of myeloperoxidase in the ELF of the lower respiratory tract, and a synergistic cytotoxic effect of alveolar inflammatory cells and ELF on lung epithelial cells, suggesting oxidants may play a role in causing the epithelial cell injury of this disorder.
对特发性肺纤维化（IPF）患者的肺炎症细胞在有和没有IPF肺泡上皮衬液（ELF）的情况下损伤51Cr标记的AKD肺泡上皮细胞的能力进行了评估。与正常情况相比，IPF细胞自发释放出过量的超氧化物（O₂）和过氧化氢（H₂O₂）（P＜0.02）。当IPF炎症细胞与自体ELF一起孵育时，AKD细胞的细胞毒性显著增加（P＜0.02）。大多数IPF患者的ELF髓过氧化物酶水平高于正常（P＜0.002）。在H₂O₂存在的情况下，将IPF ELF与AKD细胞一起孵育会导致细胞损伤增加（与对照组相比，P＜0.01），而甲硫氨酸（一种髓过氧化物酶系统清除剂）可抑制这种损伤。ELF髓过氧化物酶浓度高的IPF患者比ELF髓过氧化物酶浓度低的患者病情恶化得更快（P＜0.05）。因此，IPF的特征在于肺炎症细胞自发产生氧化剂增加、下呼吸道ELF中存在高浓度的髓过氧化物酶，以及肺泡炎症细胞和ELF对肺上皮细胞具有协同细胞毒性作用，这表明氧化剂可能在导致该疾病的上皮细胞损伤中起作用。
