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Aerosolization of recombinant SLPI to augment antineutrophil elastase protection of pulmonary epithelium.
- Source :
-
Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 1990 Nov; Vol. 69 (5), pp. 1843-8. - Publication Year :
- 1990
-
Abstract
- In a variety of lung diseases the respiratory epithelial surface must contend with an increased burden of neutrophil elastase (NE). One candidate for augmenting epithelial anti-NE protection is the secretory leukoprotease inhibitor (SLPI). In vitro evaluation demonstrated that 96 +/- 1% of the recombinant SLPI (rSLPI) molecules were capable of inhibiting NE, with an association rate constant of 7.1 +/- 0.1 X 10(6) M-1.s-1. Evaluation of rSLPI after in vitro and in vivo aerosolization showed that aerosolization did not alter rSLPI. Aerosolization of a single dose of 50 mg rSLPI to sheep resulted in a fourfold increase of the anti-NE capacity in epithelial lining fluid (ELF) at 3 h, with a half-life in ELF of 12 h. After aerosolization some rSLPI appeared in lung lymph. Simultaneous aerosolization of rSLPI and recombinant alpha 1-antitrypsin (rAAT) demonstrated a molar ratio of the concentration in lymph to the concentration in ELF 3 h after the aerosol eightfold higher for rAAT than for rSLPI. Overall, these observations demonstrate that it is feasible to use aerosolized rSLPI to directly augment the anti-NE capacity of the lung, particularly on the pulmonary epithelial surface.
- Subjects :
- Aerosols
Animals
Biological Transport
Body Fluids metabolism
Epithelium physiology
Feasibility Studies
Half-Life
Leukocyte Elastase
Leukocytes metabolism
Leukocytes physiology
Proteinase Inhibitory Proteins, Secretory
Recombinant Proteins
Serine Proteinase Inhibitors pharmacokinetics
Serine Proteinase Inhibitors pharmacology
Sheep
Structure-Activity Relationship
Lung physiology
Pancreatic Elastase antagonists & inhibitors
Proteins
Serine Proteinase Inhibitors administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 8750-7587
- Volume :
- 69
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of applied physiology (Bethesda, Md. : 1985)
- Publication Type :
- Academic Journal
- Accession number :
- 2272977
- Full Text :
- https://doi.org/10.1152/jappl.1990.69.5.1843