O'Brodovich H M, Weitz J I, Possmayer F
Department of Pediatrics, Hospital for Sick Children, Toronto, Ont., Canada.
Biol Neonate. 1990;57(6):325-33. doi: 10.1159/000243209.
Acute lung injury syndromes have many characteristics including protein-rich alveolar edema, hyaline membranes, and abnormal surface tension at the alveolar air-liquid interface. Increased surface tension can occur because of a relative surfactant deficiency and/or dysfunction. It has been previously demonstrated that surfactant dysfunction occurs when plasma protein inhibitors leak into the alveolar space during the induction of the lung injury and edema formation. The present study investigated whether inhibitors that would be generated during the stage of repair from lung injury could impair surfactant function. We determined whether fibrinogen degradation products (FDP) which would be released during lysis of the fibrin(ogen)-containing alveolar exudate and hyaline membranes, and components of the lungs' ground substance could inhibit the in vitro function of a lipid extract surfactant preparation. FDP were prepared by incubating human fibrinogen with plasmin or neutrophil elastase for 4 min to 60 h and were characterized by SDS-PAGE. Early (fragment X and Y) and late (fragment D and E) plasmin-derived FDP (MW greater than 40,000) inhibited surfactant function as assessed by a bubble surfactometer. The early elastase-derived FDP also inhibited surfactant, but the later and much smaller fragments (MW less than 15,000) did not affect surfactant function. Laminin also inhibited surfactant in a dose-dependent manner. Neither hyaluronic acid nor heparan sulfate affected surfactant performance in vitro. We conclude that plasmin-induced lysis of intraalveolar fibrinogen and hyaline membranes will result in prolonged generation (i.e. days) of surfactant inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)
急性肺损伤综合征有许多特征，包括富含蛋白质的肺泡水肿、透明膜以及肺泡气液界面处异常的表面张力。由于表面活性物质相对缺乏和/或功能障碍，可出现表面张力增加。先前已证明，在肺损伤和水肿形成诱导过程中，当血浆蛋白抑制剂漏入肺泡腔时，会发生表面活性物质功能障碍。本研究调查了肺损伤修复阶段产生的抑制剂是否会损害表面活性物质功能。我们确定在含纤维蛋白（原）的肺泡渗出物和透明膜溶解过程中释放的纤维蛋白原降解产物（FDP）以及肺间质成分是否能抑制脂质提取物表面活性物质制剂的体外功能。通过将人纤维蛋白原与纤溶酶或中性粒细胞弹性蛋白酶孵育4分钟至60小时制备FDP，并通过SDS-PAGE进行表征。通过气泡表面张力仪评估，早期（片段X和Y）和晚期（片段D和E）纤溶酶衍生的FDP（分子量大于40,000）抑制表面活性物质功能。早期弹性蛋白酶衍生的FDP也抑制表面活性物质，但后期且小得多的片段（分子量小于15,000）不影响表面活性物质功能。层粘连蛋白也以剂量依赖方式抑制表面活性物质。透明质酸和硫酸乙酰肝素在体外均不影响表面活性物质性能。我们得出结论，纤溶酶诱导的肺泡内纤维蛋白原和透明膜溶解将导致表面活性物质抑制剂的生成延长（即数天）。
