Pseudomonas aeruginosa elastase degrades surfactant proteins A and D

Am J Respir Cell Mol Biol. 2003 Apr;28(4):528-37. doi: 10.1165/rcmb.2002-0141OC.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bronchoalveolar Lavage Fluid / chemistry
  • Glycopeptides / pharmacology
  • Humans
  • Kinetics
  • Lung / metabolism
  • Lung / pathology
  • Lung Transplantation / physiology
  • Pancreatic Elastase / metabolism*
  • Protease Inhibitors / pharmacology
  • Pseudomonas aeruginosa / enzymology*
  • Pulmonary Surfactant-Associated Protein A / isolation & purification
  • Pulmonary Surfactant-Associated Protein A / metabolism*
  • Pulmonary Surfactant-Associated Protein D / isolation & purification
  • Pulmonary Surfactant-Associated Protein D / metabolism*
  • Thermodynamics


  • Glycopeptides
  • Protease Inhibitors
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactant-Associated Protein D
  • Pancreatic Elastase
  • phosphoramidon