Abstract
Antileucoprotease (ALP), a potent inhibitor of human neutrophil elastase (HNE), may be a modulating factor in the pathogenesis of emphysema. Investigating the clearance of intratracheally-instilled ALP in hamsters, we observed a rapid clearance from the airway lumen within 60 min, whereafter the remaining 40% slowly decreased with a calculated half-life (T0.5) of 2.8 h. Lung tissue-associated ALP showed a peak at 40 min and slowly decreased (T0.5 approximately 3 h). In vivo efficacy of ALP on HNE-induced pulmonary lesions was studied by instillation of either 365 micrograms or 730 micrograms ALP, followed after 1 h by 420 micrograms HNE. Emphysema, haemorrhage and secretory cell metaplasia (SCM) were quantified 21 days after instillations. ALP was found to be able to inhibit emphysema and haemorrhage in a dose-related way, the decrease of haemorrhage being less pronounced. SCM was minimally affected. These results show that ALP inhibits efficiently the development of HNE-induced emphysema and, to a lesser extent, haemorrhage. We speculate that tissue-associated ALP might be responsible for this protection.
