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.

This article has been cited by other articles:

				T. Iizuka, Y. Ishii, K. Itoh, T. Kiwamoto, T. Kimura, Y. Matsuno, Y. Morishima, A. E. Hegab, S. Homma, A. Nomura, et al. Nrf2-deficient mice are highly susceptible to cigarette smoke-induced emphysema Genes Cells, December 1, 2005; 10(12): 1113 - 1125. [Abstract] [Full Text] [PDF]

				A. B. Lentsch, J. A. Jordan, B. J. Czermak, K. M. Diehl, E. M. Younkin, V. Sarma, and P. A. Ward Inhibition of NF-{kappa}B Activation and Augmentation of I{kappa}Bß by Secretory Leukocyte Protease Inhibitor during Lung Inflammation Am. J. Pathol., January 1, 1999; 154(1): 239 - 247. [Abstract] [Full Text] [PDF]

				N. Shine, K. Konopka, and N. Duzgunes Concise Review: The Anti-HIV-1 Activity Associated with Saliva Journal of Dental Research, February 1, 1997; 76(2): 634 - 640. [Abstract] [PDF]