Pseudomonas aeruginosa elastase degrades surfactant proteins A and D.
Both in vitro and in vivo studies provide evidence that surfactant protein (SP)-A and SP-D have an important role in the innate immune response to Pseudomonas aeruginosa. In preliminary experiments characterizing the binding of SP-A to this bacteria, we observed the appearance of apparent degradation products of SP-A, and therefore we hypothesized that P. aeruginosa produces an enzyme that degrades SP-A. Incubation of SP-A with P. aeruginosa organisms from several clinical isolates resulted in concentration- and temperature-dependent degradation of SP-A that was inhibited by a metalloproteinase inhibitor, phosphoramidon. The degradative enzyme was purified by anion exchange chromatography and identified by ion trap mass spectroscopy as Pseudomonas elastase, which was shown to directly degrade SP-A and SP-D. Incubation of P. aeruginosa or purified elastase with cell-free bronchoalveolar lavage (BAL) resulted in degradation of SP-A. Furthermore, SP-A degradation fragments were detectable in BAL from lung transplant patients with cystic fibrosis. We speculate that degradation of SP-A and SP-D is a virulence mechanism in the pathogenesis of chronic P. aeruginosa infection.
Duke Scholars
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Related Subject Headings
- Thermodynamics
- Respiratory System
- Pulmonary Surfactant-Associated Protein D
- Pulmonary Surfactant-Associated Protein A
- Pseudomonas aeruginosa
- Protease Inhibitors
- Pancreatic Elastase
- Lung Transplantation
- Lung
- Kinetics
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Thermodynamics
- Respiratory System
- Pulmonary Surfactant-Associated Protein D
- Pulmonary Surfactant-Associated Protein A
- Pseudomonas aeruginosa
- Protease Inhibitors
- Pancreatic Elastase
- Lung Transplantation
- Lung
- Kinetics