Intratracheally-instilled antileukoprotease and alpha 1-proteinase inhibitor: effect on human neutrophil elastase-induced experimental emphysema and pulmonary localization.

The Histochemical Journal Pub Date : 1994-10-01
A Rudolphus, J A Kramps, I Mauve, J H Dijkman
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Abstract

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.

气管内灌注抗白蛋白酶和α 1蛋白酶抑制剂对中性粒细胞弹性酶诱导的实验性肺气肿和肺定位的影响。
比较了气管内灌注抗白细胞蛋白酶和α 1蛋白酶抑制剂对人中性粒细胞弹性蛋白酶(HNE)致小鼠肺损伤的保护作用。在HNE注射前20小时以等摩尔量滴注抗蛋白酶。在所有时间间隔,两种抑制剂都能有效地抑制hne诱导的肺气肿。在HNE滴注前1小时,α 1蛋白酶抑制剂比抗白蛋白酶更有效。α 1-蛋白酶抑制剂在HNE发作前1 ~ 12 h滴注,可有效抑制HNE引起的出血,而抗白细胞蛋白酶仅在HNE发作前1 h滴注时才有保护作用。仅当两种抑制剂在HNE前1小时灌注时才影响分泌细胞化生的发生。在第二个系列实验中,采用间接免疫荧光技术研究了两种抗蛋白酶在仓鼠气管内滴注后的定位。在安装后20小时,抗白蛋白蛋白酶被发现在所有时间点都与弹性蛋白纤维相关。相比之下,α - 1蛋白酶抑制剂被观察到位于肺泡内壁和弥漫性肺泡肺组织在所有时间点的研究。没有发现抑制剂与弹性蛋白纤维的关联。我们得出结论,与弹性纤维相关的抗白蛋白蛋白酶的部分可能在保护hne诱导的肺气肿中起重要作用。
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