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Effect of the elastase inhibitor, eglin-c, on antibacterial mechanisms in experimental pneumonia. Description of a system to quantitate phagocytic and bactericidal activity of resident murine alveolar macrophages in vivo.

Abstract
To evaluate the influence of the elastase inhibitor, eglin-c, on lung host defense, normal CD-1 mice were challenged intratracheally with type 3 Streptococcus pneumoniae suspended in phosphate-buffered saline alone or containing 10 mg/ml eglin-c. After infection with 5 X 10(3) colony-forming units (cfu), animals given eglin-c demonstrated a significant enhancement in their capacity to clear viable pneumococci from the lungs at 24 h after challenge; the augmented pulmonary clearance was associated with an increased influx of granulocytes at 6 and 24 h. After challenge with higher inocula (5 X 10(4) and 5 X 10(5) cfu), animals treated with eglin-c exhibited a significant impairment in pulmonary clearance at 6 h; however, in the presence of larger numbers of granulocytes within the bronchoalveolar spaces, the attenuation in pulmonary clearance resolved between 6 and 24 h. Changes in the kinetics of pulmonary clearance that were similar to those noted after infection with high pneumococcal inocula were also observed after challenge with 1 X 10(6) cfu Staphylococcus aureus. In addition, although it did not influence the in vivo phagocytic capacity of resident alveolar against S. aureus, eglin-c depressed the bactericidal activity of these cells. We conclude that in the mouse, high doses of eglin-c alter pulmonary antimicrobial mechanisms important for preventing and eradicating bacterial infection of the lower respiratory tract.
AuthorsA L Esposito, L A Quinn, E C Lucey, G L Snider
JournalThe American review of respiratory disease (Am Rev Respir Dis) Vol. 135 Issue 3 Pg. 676-81 (Mar 1987) ISSN: 0003-0805 [Print] United States
PMID3644606 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Proteins
  • Serpins
  • eglin proteinase inhibitors
  • Pancreatic Elastase
Topics
  • Animals
  • Blood Bactericidal Activity
  • Female
  • Lung (immunology, microbiology)
  • Macrophages (physiology)
  • Mice
  • Mice, Inbred Strains
  • Pancreatic Elastase (antagonists & inhibitors)
  • Phagocytosis
  • Pneumonia, Pneumococcal (etiology, immunology, microbiology, pathology)
  • Proteins (therapeutic use)
  • Pulmonary Alveoli (cytology, pathology, physiology)
  • Serpins

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