Intravenous recombinant secretory leukoprotease inhibitor augments antineutrophil elastase defense. Academic Article uri icon

Overview

MeSH

  • Animals
  • Blotting, Western
  • Chromatography, High Pressure Liquid
  • Electrophoresis, Polyacrylamide Gel
  • Epithelium
  • Female
  • Injections, Intravenous
  • Lung
  • Proteinase Inhibitory Proteins, Secretory
  • Recombinant Proteins
  • Sheep

MeSH Major

  • Neutrophils
  • Pancreatic Elastase
  • Proteins
  • Serine Proteinase Inhibitors

abstract

  • Secretory leukoprotease inhibitor (SLPI), a 12-kDa serine antiprotease, normally protects the upper airway epithelial surface from attack by neutrophil elastase (NE). In the context that a variety of inflammatory lung diseases are characterized by large neutrophil burdens with resultant high levels of NE in the lung, recombinant SLPI (rSLPI), a molecule identical to natural SLPI, may be an effective means to augment the anti-NE protective screen of the lung. To determine whether intravenous rSLPI will augment respiratory tract and epithelial surface levels of SLPI and anti-NE capacity, rSLPI was administered intravenously to sheep and SLPI levels were quantified in plasma, lung lymph (as a measure of lung interstitial levels), lung epithelial lining fluid (ELF), and urine. rSLPI (1 g) was administered over 10 min, and after 30 min plasma levels of SLPI were 8 microM and decreased with a half-life of 1.8 h. Lymph SLPI levels paralleled the plasma levels: 4 h after infusion the lymph-to-plasma ratio was 0.8. ELF SLPI levels paralleled the lymph levels: 4 h after infusion the ELF-to-lymph ratio was 0.3. Western analysis demonstrated intact SLPI in lymph and ELF, and functional analysis showed increases in lymph and ELF anti-NE capacity that paralleled the levels of SLPI. As might be expected from a protein with a molecular mass of 12 kDa, urine excretion was high, with 20% of the SLPI excreted over 5 h. However, if the rate of infusion was slowed, SLPI excretion decreased significantly, with a 3-h infusion associated with 9% excretion and a 12-h infusion associated with less than 0.2% excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

publication date

  • July 1992

has subject area

  • Animals
  • Blotting, Western
  • Chromatography, High Pressure Liquid
  • Electrophoresis, Polyacrylamide Gel
  • Epithelium
  • Female
  • Injections, Intravenous
  • Lung
  • Neutrophils
  • Pancreatic Elastase
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins
  • Recombinant Proteins
  • Serine Proteinase Inhibitors
  • Sheep

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 1354669

Additional Document Info

start page

  • 317

end page

  • 323

volume

  • 73

number

  • 1