Recombinant secretory leukoprotease inhibitor augments glutathione levels in lung epithelial lining fluid

A. Gillissen, P. Birrer, N. G. McElvaney, R. Buhl, C. Vogelmeier, R. F. Hoyt, R. C. Hubbard, Ronald Crystal

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Secretory leukoprotease inhibitor (SLPI), a 12-kDa serine antiprotease, serves as the major inhibitor of neutrophil elastase (NE) on the epithelial surface of the upper airways. As a control for studies to evaluate the aerosol administration of recombinant SLPI (rSLPI) to augment the anti-NE defenses of the lung, the status of antioxidants in respiratory epithelial lining fluid (ELF) was evaluated. Unexpectedly, aerosol administration of rSLPI caused an elevation in ELF glutathione, a major component of the epithelial antioxidant screen; i.e., rSLPI may provide not only augmentation of anti-NE defenses but also antioxidant defenses. To evaluate this concept, rSLPI (100 mg) was aerosolized to sheep, and SLPI, glutathione, anti-NE capacity, and anti-H2O2 capacity were evaluated in respiratory ELF over a 30-h period. As expected, aerosolization of rSLPI increased ELF SLPI levels and anti-NE capacity. Strikingly, postaerosol levels of glutathione in ELF were also increased (5-fold 24 h after aerosol), with a concomitant increase in ELF anti-H2O2 capacity; i.e., the rSLPI augmented the antioxidant screen of ELF. This suggests that rSLPI may be particularly well suited for therapy in lung diseases characterized by excess of both serine proteases and oxidants on the respiratory epithelial surface.

Original languageEnglish
Pages (from-to)825-832
Number of pages8
JournalJournal of Applied Physiology
Volume75
Issue number2
Publication statusPublished - 1 Jan 1993
Externally publishedYes

Fingerprint

Secretory Leukocyte Peptidase Inhibitor
Leukocyte Elastase
Glutathione
Antioxidants
Aerosols
Lung
Secretory Proteinase Inhibitory Proteins
Serine Proteases
Protease Inhibitors
Oxidants
Serine
Lung Diseases
Sheep

Keywords

  • animal
  • antioxidants
  • antiproteases
  • bronchoscopy

ASJC Scopus subject areas

  • Endocrinology
  • Physiology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Gillissen, A., Birrer, P., McElvaney, N. G., Buhl, R., Vogelmeier, C., Hoyt, R. F., ... Crystal, R. (1993). Recombinant secretory leukoprotease inhibitor augments glutathione levels in lung epithelial lining fluid. Journal of Applied Physiology, 75(2), 825-832.

Recombinant secretory leukoprotease inhibitor augments glutathione levels in lung epithelial lining fluid. / Gillissen, A.; Birrer, P.; McElvaney, N. G.; Buhl, R.; Vogelmeier, C.; Hoyt, R. F.; Hubbard, R. C.; Crystal, Ronald.

In: Journal of Applied Physiology, Vol. 75, No. 2, 01.01.1993, p. 825-832.

Research output: Contribution to journalArticle

Gillissen, A, Birrer, P, McElvaney, NG, Buhl, R, Vogelmeier, C, Hoyt, RF, Hubbard, RC & Crystal, R 1993, 'Recombinant secretory leukoprotease inhibitor augments glutathione levels in lung epithelial lining fluid', Journal of Applied Physiology, vol. 75, no. 2, pp. 825-832.
Gillissen A, Birrer P, McElvaney NG, Buhl R, Vogelmeier C, Hoyt RF et al. Recombinant secretory leukoprotease inhibitor augments glutathione levels in lung epithelial lining fluid. Journal of Applied Physiology. 1993 Jan 1;75(2):825-832.
Gillissen, A. ; Birrer, P. ; McElvaney, N. G. ; Buhl, R. ; Vogelmeier, C. ; Hoyt, R. F. ; Hubbard, R. C. ; Crystal, Ronald. / Recombinant secretory leukoprotease inhibitor augments glutathione levels in lung epithelial lining fluid. In: Journal of Applied Physiology. 1993 ; Vol. 75, No. 2. pp. 825-832.
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