Aerosolization of recombinant SLPI to augment antineutrophil elastase protection of pulmonary epithelium.
| Publication Type | Academic Article |
| Authors | Vogelmeier C, Buhl R, Hoyt R, Wilson E, Fells G, Hubbard R, Schnebli H, Thompson R, Crystal R |
| Journal | J Appl Physiol (1985) |
| Volume | 69 |
| Issue | 5 |
| Pagination | 1843-8 |
| Date Published | 11/01/1990 |
| ISSN | 8750-7587 |
| Keywords | Lung, Pancreatic Elastase, Proteins, Serine Proteinase Inhibitors |
| 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. |
| DOI | 10.1152/jappl.1990.69.5.1843 |
| PubMed ID | 2272977 |