Functional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases.

Hdl Handle:
http://hdl.handle.net/10147/126575
Title:
Functional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases.
Authors:
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
Affiliation:
Department of Medicine, Pulmonary Research Division, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.
Citation:
Functional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases. 2010, 391 (6):705-16 Biol. Chem.
Journal:
Biological chemistry
Issue Date:
Jun-2010
URI:
http://hdl.handle.net/10147/126575
DOI:
10.1515/BC.2010.066
PubMed ID:
20370321
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.
Item Type:
Article
Language:
en
MeSH:
Bacterial Proteins; Blotting, Western; Chromatography, High Pressure Liquid; Elafin; Electrophoresis, Polyacrylamide Gel; Fibronectins; Humans; Mass Spectrometry; Metalloproteases; Pseudomonas aeruginosa
ISSN:
1437-4315

Full metadata record

DC FieldValue Language
dc.contributor.authorGuyot, Nicolasen
dc.contributor.authorBergsson, Gudmunduren
dc.contributor.authorButler, Marcus Wen
dc.contributor.authorGreene, Catherine Men
dc.contributor.authorWeldon, Sinéaden
dc.contributor.authorKessler, Efraten
dc.contributor.authorLevine, Rodney Len
dc.contributor.authorO'Neill, Shane Jen
dc.contributor.authorTaggart, Clifford Cen
dc.contributor.authorMcElvaney, Noel Gen
dc.date.accessioned2011-03-31T13:19:18Z-
dc.date.available2011-03-31T13:19:18Z-
dc.date.issued2010-06-
dc.identifier.citationFunctional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases. 2010, 391 (6):705-16 Biol. Chem.en
dc.identifier.issn1437-4315-
dc.identifier.pmid20370321-
dc.identifier.doi10.1515/BC.2010.066-
dc.identifier.urihttp://hdl.handle.net/10147/126575-
dc.description.abstractElafin 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.-
dc.language.isoenen
dc.subject.meshBacterial Proteins-
dc.subject.meshBlotting, Western-
dc.subject.meshChromatography, High Pressure Liquid-
dc.subject.meshElafin-
dc.subject.meshElectrophoresis, Polyacrylamide Gel-
dc.subject.meshFibronectins-
dc.subject.meshHumans-
dc.subject.meshMass Spectrometry-
dc.subject.meshMetalloproteases-
dc.subject.meshPseudomonas aeruginosa-
dc.titleFunctional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medicine, Pulmonary Research Division, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.en
dc.identifier.journalBiological chemistryen
dc.description.provinceLeinster-

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