Functional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases
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Nicolas Guyot
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.
©2010 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Guest Editorial
- Highlight: Molecular Neurobiology
- HIGHLIGHT: MOLECULAR NEUROBIOLOGY
- Actin-mediated gene expression in neurons: the MRTF-SRF connection
- RIM proteins and their role in synapse function
- Brain tumor stem cells
- The mitochondria permeability transition pore complex in the brain with interacting proteins – promising targets for protection in neurodegenerative diseases
- Involvement of the calcium sensor GCAP1 in hereditary cone dystrophies
- Live cell imaging of cytoskeletal dynamics in neurons using fluorescence photoactivation
- REVIEWS
- Contributions of the Ah receptor to bilirubin homeostasis and its antioxidative and atheroprotective functions
- Cathepsin L in metastatic bone disease: therapeutic implications
- GENES AND NUCLEIC ACIDS
- Activity-based selection of HIV-1 reverse transcriptase variants with decreased polymerization fidelity
- CELL BIOLOGY AND SIGNALING
- Multiple protective functions of catalase against intercellular apoptosis-inducing ROS signaling of human tumor cells
- Molecular characterisation of ‘transmembrane protein 192’ (TMEM192), a novel protein of the lysosomal membrane
- PROTEOLYSIS
- Functional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases
