Effect of human antileucoprotease on experimental emphysema.
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.
Rudolphus
A
A
Dept of Pulmonology, University Hospital Leiden, The Netherlands.
Kramps
J A
JA
Dijkman
J H
JH
D000818:Animals; D006224:Cricetinae; D006207:Half-Life; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D019272:Leukocyte Elastase; D008168:Lung / Q000187:drug effects; D008171:Lung Diseases / Q000517:prevention & control; D010196:Pancreatic Elastase / Q000009:adverse effects / Q000037:antagonists & inhibitors; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000517:prevention & control*; D015842:Serine Proteinase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution
D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D015842:Serine Proteinase Inhibitors; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase