Aerosolization of recombinant SLPI to augment antineutrophil elastase protection of pulmonary epithelium. Academic Article uri icon

Overview

MeSH

  • Aerosols
  • Animals
  • Biological Transport
  • Body Fluids
  • Epithelium
  • Feasibility Studies
  • Half-Life
  • Leukocyte Elastase
  • Leukocytes
  • Proteinase Inhibitory Proteins, Secretory
  • Recombinant Proteins
  • Sheep
  • Structure-Activity Relationship

MeSH Major

  • 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.

publication date

  • November 1990

has subject area

  • Aerosols
  • Animals
  • Biological Transport
  • Body Fluids
  • Epithelium
  • Feasibility Studies
  • Half-Life
  • Leukocyte Elastase
  • Leukocytes
  • Lung
  • Pancreatic Elastase
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins
  • Recombinant Proteins
  • Serine Proteinase Inhibitors
  • Sheep
  • Structure-Activity Relationship

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 2272977

Additional Document Info

start page

  • 1843

end page

  • 1848

volume

  • 69

number

  • 5