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

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.