Functional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases.
Guyot, Nicolas Bergsson, Gudmundur Butler, Marcus W Greene, Catherine M Weldon, Sinéad Kessler, Efrat Levine, Rodney L O'Neill, Shane J Taggart, Clifford C McElvaney, Noel G
Guyot, Nicolas
Bergsson, Gudmundur
Butler, Marcus W
Greene, Catherine M
Weldon, Sinéad
Kessler, Efrat
Levine, Rodney L
O'Neill, Shane J
Taggart, Clifford C
McElvaney, Noel G
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Advisors
Editors
Other Contributors
Departments
Department of Medicine, Pulmonary Research Division, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.
Date
2010-06
Date Submitted
Keywords
Other Subjects
Subject Mesh
Bacterial Proteins
Blotting, Western
Chromatography, High Pressure Liquid
Elafin
Electrophoresis, Polyacrylamide Gel
Fibronectins
Humans
Mass Spectrometry
Metalloproteases
Pseudomonas aeruginosa
Blotting, Western
Chromatography, High Pressure Liquid
Elafin
Electrophoresis, Polyacrylamide Gel
Fibronectins
Humans
Mass Spectrometry
Metalloproteases
Pseudomonas aeruginosa
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
Abstract
Elafin is a 6-kDa innate immune protein present at several epithelial surfaces including the pulmonary epithelium. It is a canonical protease inhibitor of two neutrophil serine proteases [neutrophil elastase (NE) and proteinase 3] with the capacity to covalently bind extracellular matrix proteins by transglutamination. In addition to these properties, elafin also possesses antimicrobial and immunomodulatory activities. The aim of the present study was to investigate the effect of Pseudomonas aeruginosa proteases on elafin function. We found that P. aeruginosa PAO1-conditioned medium and two purified Pseudomonas metalloproteases, pseudolysin (elastase) and aeruginolysin (alkaline protease), are able to cleave recombinant elafin. Pseudolysin was shown to inactivate the anti-NE activity of elafin by cleaving its protease-binding loop. Interestingly, antibacterial properties of elafin against PAO1 were found to be unaffected after pseudolysin treatment. In contrast to pseudolysin, aeruginolysin failed to inactivate the inhibitory properties of elafin against NE. Aeruginolysin cleaves elafin at the amino-terminal Lys6-Gly7 peptide bond, resulting in a decreased ability to covalently bind purified fibronectin following transglutaminase activity. In conclusion, this study provides evidence that elafin is susceptible to proteolytic cleavage at alternative sites by P. aeruginosa metalloproteinases, which can affect different biological functions of elafin.
Language
en
ISSN
1437-4315
eISSN
ISBN
DOI
10.1515/BC.2010.066
PMID
20370321