Rudolphus A, Kramps J A, Mauve I, Dijkman J H
University Hospital Leiden, Department of Pulmonology, The Netherlands.
Histochem J. 1994 Oct;26(10):817-24.
The protective capacities of intratracheally-instilled antileukoprotease and alpha 1-proteinase inhibitor towards human neutrophil elastase (HNE)-induced pulmonary injuries were compared in hamsters. The antiproteases were instilled in equimolar amounts up to 20 h before HNE instillation. At all intervals, both inhibitors were able to inhibit HNE-induced emphysema efficiently. At 1 h before HNE instillation, alpha 1-proteinase inhibitor was more effective in this regard than antileukoprotease. alpha 1-Proteinase inhibitor, instilled 1 to 12 h before HNE, efficiently inhibited HNE-induced haemorrhage, while the antileukoprotease protected haemorrhage only when it was administered 1 h before HNE. The development of secretory cell metaplasia was affected only when both inhibitors were instilled 1 h before HNE. In a second series of experiments, the localization of the two antiproteases after intratracheal instillation in hamster was investigated using an indirect immunofluorescence technique. Up to 20 h after installation, antileukoprotease was found to be associated with elastin fibres at all points of time investigated. In contrast, alpha 1-proteinase inhibitor was observed to be located in the alveolar lining and diffusely in the alveolar lung tissue at all points of time investigated. No association of the inhibitor with elastin fibres was found. We conclude that the fraction of antileukoprotease associated with the elastic fibre may be important in the protection of HNE-induced pulmonary emphysema.
在仓鼠中比较了气管内注入抗白细胞蛋白酶和α1-蛋白酶抑制剂对人中性粒细胞弹性蛋白酶（HNE）诱导的肺损伤的保护能力。在注入HNE前长达20小时以等摩尔量注入抗蛋白酶。在所有时间间隔，两种抑制剂均能有效抑制HNE诱导的肺气肿。在注入HNE前1小时，α1-蛋白酶抑制剂在这方面比抗白细胞蛋白酶更有效。在注入HNE前1至12小时注入α1-蛋白酶抑制剂能有效抑制HNE诱导的出血，而抗白细胞蛋白酶仅在注入HNE前1小时给药时才能保护出血。仅当两种抑制剂均在注入HNE前1小时注入时，分泌细胞化生的发展才受到影响。在第二系列实验中，使用间接免疫荧光技术研究了仓鼠气管内注入后两种抗蛋白酶的定位。在注入后长达20小时，在所研究的所有时间点均发现抗白细胞蛋白酶与弹性纤维相关。相比之下，在所研究的所有时间点均观察到α1-蛋白酶抑制剂位于肺泡内衬并在肺泡肺组织中呈弥漫性分布。未发现该抑制剂与弹性纤维相关。我们得出结论，与弹性纤维相关的抗白细胞蛋白酶部分可能在保护HNE诱导的肺气肿中起重要作用。
