title: Pseudomonas aeruginosa elastase degrades surfactant proteins A and D.
abstract: 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.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: William I
authors.initials: WI
authors.lastname: Mariencheck
authors.forename: John F
authors.initials: JF
authors.lastname: Alcorn
authors.forename: Scott M
authors.initials: SM
authors.lastname: Palmer
authors.forename: Jo Rae
authors.initials: JR
authors.lastname: Wright
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000378:metabolism / Q000473:pathology; D016040:Lung Transplantation / Q000502:physiology; D010196:Pancreatic Elastase / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000302:isolation & purification / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000302:isolation & purification / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D006020:Glycopeptides; D011480:Protease Inhibitors; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D010196:Pancreatic Elastase; C008890:phosphoramidon