Effect of varying the time interval between intratracheal administration of eglin-c and human neutrophil elastase on prevention of emphysema and secretory cell metaplasia in hamsters. With observations on the fate of eglin-c and the effect of repeated instillations.

Abstract

Eglin-c is a naturally occurring polypeptide of 70 amino acids with a molecular mass of 8,100 daltons. It is a strong inhibitor of human neutrophil elastase (HNE) and cathepsin-G, and, when given intratracheally to hamsters 1 h before human neutrophil elastase, it can prevent or ameliorate the emphysema produced by HNE. The present experiments were designed to determine the duration of the effectiveness of eglin-c, prepared by DNA technology from Escherichia coli, in preventing the emphysema and secretory cell metaplasia induced by HNE. Eglin-c (2,000 micrograms in 0.5 ml saline) was effective in ameliorating emphysema, as determined histologically and physiologically, when it was given intratracheally to hamsters 1, 2, 4, and 8 h before the intratracheal instillation of 300 micrograms of HNE. Eglin-c ameliorated bronchial secretory cell metaplasia when given 1 h before HNE but not when the time intervals were 2 h or longer. The clearance of [3H]eglin-c from the lungs was assessed. Four h after intratracheal instillation of 446 micrograms of [3H]eglin-c, 33% of the tritium was found in the lung tissue and bronchoalveolar lavage fluid; 83% of the radioactivity in the lavage fluid supernatant was associated with functionally active eglin-c. No evidence of bronchopulmonary toxicity was seen in hamsters given 4 intratracheal instillations of 2,000 micrograms of eglin-c at 1-wk intervals.

• Authors: E C Lucey, P J Stone, T G Christensen, R Breuer, J D Calore, G L Snider
• Journal: The American review of respiratory disease (Am Rev Respir Dis) Vol. 134 Issue 3 Pg. 471-5 (Sep 1986) ISSN: 0003-0805 [Print] United States
• PMID: 3530070 (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

• Protease Inhibitors
• Proteins
• Serpins
• eglin proteinase inhibitors
• Pancreatic Elastase

Topics

• Animals
• Bronchi (drug effects, metabolism, pathology)
• Cricetinae
• Humans
• Lung (metabolism, pathology)
• Male
• Mesocricetus
• Metaplasia
• Neutrophils (enzymology)
• Pancreatic Elastase (toxicity)
• Protease Inhibitors (administration & dosage)
• Proteins (administration & dosage, metabolism, toxicity)
• Pulmonary Emphysema (metabolism, pathology, prevention & control)
• Serpins
• Trachea