Recombinant secretory leukoprotease inhibitor augments glutathione levels in lung epithelial lining fluid. Academic Article uri icon

Overview

MeSH

  • Aerosols
  • Animals
  • Cysteine
  • Epithelium
  • In Vitro Techniques
  • Neutrophils
  • Oxidation-Reduction
  • Pancreatic Elastase
  • Proteinase Inhibitory Proteins, Secretory
  • Recombinant Proteins
  • Sheep

MeSH Major

  • Glutathione
  • Lung
  • Proteins
  • Serine Proteinase Inhibitors

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.

publication date

  • August 1993

has subject area

  • Aerosols
  • Animals
  • Cysteine
  • Epithelium
  • Glutathione
  • In Vitro Techniques
  • Lung
  • Neutrophils
  • Oxidation-Reduction
  • Pancreatic Elastase
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins
  • Recombinant Proteins
  • Serine Proteinase Inhibitors
  • Sheep

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 7901193

Additional Document Info

start page

  • 825

end page

  • 832

volume

  • 75

number

  • 2