Aerosolization of recombinant SLPI to augment antineutrophil elastase protection of pulmonary epithelium

C. Vogelmeier, R. Buhl, R. F. Hoyt, E. Wilson, G. A. Fells, R. C. Hubbard, H. P. Schnebli, R. C. Thompson, Ronald Crystal

Research output: Contribution to journalArticle

54 Citations (Scopus)

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 106 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 α1-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.

Original languageEnglish
Pages (from-to)1843-1848
Number of pages6
JournalJournal of Applied Physiology
Volume69
Issue number5
Publication statusPublished - 1 Dec 1990
Externally publishedYes

Fingerprint

Secretory Leukocyte Peptidase Inhibitor
Leukocyte Elastase
Pancreatic Elastase
Epithelium
Lung
Lymph
Lung Volume Measurements
Aerosols
Lung Diseases
Half-Life
Sheep

Keywords

  • aerosol
  • antielastase
  • recombinant protein
  • secretory leukoprotease inhibitor

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Vogelmeier, C., Buhl, R., Hoyt, R. F., Wilson, E., Fells, G. A., Hubbard, R. C., ... Crystal, R. (1990). Aerosolization of recombinant SLPI to augment antineutrophil elastase protection of pulmonary epithelium. Journal of Applied Physiology, 69(5), 1843-1848.

Aerosolization of recombinant SLPI to augment antineutrophil elastase protection of pulmonary epithelium. / Vogelmeier, C.; Buhl, R.; Hoyt, R. F.; Wilson, E.; Fells, G. A.; Hubbard, R. C.; Schnebli, H. P.; Thompson, R. C.; Crystal, Ronald.

In: Journal of Applied Physiology, Vol. 69, No. 5, 01.12.1990, p. 1843-1848.

Research output: Contribution to journalArticle

Vogelmeier, C, Buhl, R, Hoyt, RF, Wilson, E, Fells, GA, Hubbard, RC, Schnebli, HP, Thompson, RC & Crystal, R 1990, 'Aerosolization of recombinant SLPI to augment antineutrophil elastase protection of pulmonary epithelium', Journal of Applied Physiology, vol. 69, no. 5, pp. 1843-1848.
Vogelmeier C, Buhl R, Hoyt RF, Wilson E, Fells GA, Hubbard RC et al. Aerosolization of recombinant SLPI to augment antineutrophil elastase protection of pulmonary epithelium. Journal of Applied Physiology. 1990 Dec 1;69(5):1843-1848.
Vogelmeier, C. ; Buhl, R. ; Hoyt, R. F. ; Wilson, E. ; Fells, G. A. ; Hubbard, R. C. ; Schnebli, H. P. ; Thompson, R. C. ; Crystal, Ronald. / Aerosolization of recombinant SLPI to augment antineutrophil elastase protection of pulmonary epithelium. In: Journal of Applied Physiology. 1990 ; Vol. 69, No. 5. pp. 1843-1848.
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