Document Detail


Inhibition of human neutrophil elastase-induced acute lung injury in hamsters by recombinant human pre-elafin (trappin-2).
MedLine Citation:
PMID:  11834675     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
STUDY OBJECTIVES: Pre-elafin, also known as trappin-2, is an elastase-specific inhibitor that could be an ideal candidate for the treatment of neutrophil elastase-driven lung diseases. The inhibitory activity of pre-elafin resides in the COOH-terminal region that can be released as mature elafin. The NH(2)-terminal moiety of pre-elafin is characterized by the presence of a specific repeating sequence, termed cementoin, believed to immobilize the inhibitor to lung protein components and restrict its diffusion from the desired sites of action. This property should confer an advantage to pre-elafin compared to elafin in the treatment of neutrophil elastase-driven lung diseases. MEASUREMENTS: The inhibitory effect of recombinant human pre-elafin was assessed in a human neutrophil elastase-induced acute lung injury model in Golden Syrian hamsters. BAL fluid hemoglobin content was used as a marker of lung injury. RESULTS: Recombinant human pre-elafin administered intratracheally 1 h prior to neutrophil elastase dose-dependently inhibited the lung hemorrhage with a calculated half-effective dose of 8.1 microg/kg (0.7 nmol/kg). Pre-elafin was equally efficient when administered 3 h before neutrophil elastase. In contrast to pre-elafin, commercial synthetic elafin was ineffective in inhibiting neutrophil elastase-induced lung hemorrhage even at a dose of 4.45 nmol/kg. CONCLUSIONS: Our results suggest that pre-elafin may be eventually used in the treatment of neutrophil elastase-driven lung diseases.
Authors:
Guy M Tremblay; Eric Vachon; Chantal Larouche; Yves Bourbonnais
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Chest     Volume:  121     ISSN:  0012-3692     ISO Abbreviation:  Chest     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-02-08     Completed Date:  2002-03-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0231335     Medline TA:  Chest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  582-8     Citation Subset:  AIM; IM    
Affiliation:
Unité de recherche, Hôpital Laval, Institut universitaire de cardiologie et de pneumologie de l'Université Laval, Sainte-Foy, Quebec, Canada. guy.tremblay@med.ulaval.edu
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Animals
Bronchoalveolar Lavage Fluid / chemistry
Cricetinae
Hemoglobins / analysis
Hemorrhage / prevention & control*
Leukocyte Elastase / antagonists & inhibitors*
Lung Diseases / prevention & control*
Proteinase Inhibitory Proteins, Secretory
Proteins / therapeutic use*
Recombinant Proteins / therapeutic use
Serine Proteinase Inhibitors / therapeutic use*
Chemical
Reg. No./Substance:
0/Hemoglobins; 0/Proteinase Inhibitory Proteins, Secretory; 0/Proteins; 0/Recombinant Proteins; 0/Serine Proteinase Inhibitors; EC 3.4.21.37/Leukocyte Elastase
Comments/Corrections
Erratum In:
Chest 2002 Jun;121(6):2085

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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