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Am J Physiol Lung Cell Mol Physiol (October 29, 2004). doi:10.1152/ajplung.00322.2004
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Submitted on August 26, 2004
Accepted on October 25, 2004

Pseudomonas aeruginosa protease IV degrades surfactant proteins and inhibits surfactant host defense and biophysical functions

Jaret L. Malloy1, Ruud A.W. Veldhuizen2, Brett A. Thibodeaux3, Richard J. O'Callaghan3, and Jo Rae Wright1*

1 Department of Cell Biology, Duke University Medical Center, Durham, NC, USA
2 Department of Physiology and Pharmacology and Medicine, Lawson Health Research Institute, University of Western Ontario, London, ON, Canada
3 Department of Microbiology, Immunology, and Parasitology, LSU Medical Center, New Orleans, LA, USA

* To whom correspondence should be addressed. E-mail: j.wright{at}cellbio.duke.edu.

Pulmonary surfactant has two distinct functions within the lung; reduction of surface tension at the air-liquid interface and participation in innate host defense. Both functions are dependent on surfactant-associated proteins. Pseudomonas aeruginosa is primarily responsible for respiratory dysfunction and death in cystic fibrosis patients and is also a leading pathogen in nosocomial pneumonia. P. aeruginosa secretes a number of proteases that contribute to its virulence. We hypothesized that P. aeruginosa protease IV degrades surfactant proteins and results in a reduction in pulmonary surfactant host defense and biophysical functions. Protease IV was isolated from cultured supernatant of P. aeruginosa by gel chromatography. Incubation of cell-free bronchoalveolar lavage fluid (BALF) with protease IV resulted in degradation of SP-A, SP-D and SP-B. Surfactant proteins were degraded in a time- and dose-dependent fashion by protease IV and degradation was inhibited by the trypsin-like serine protease inhibitor N-{alpha}-p-tosyl-Lchloromethyl ketone (TLCK). Degradation by protease IV inhibited SP-A and SP-Dmediated bacterial aggregation and uptake by macrophages. Surfactant treated with protease IV was unable to reduce surface tension as effectively as untreated surfactant and this effect was inhibited by TLCK. We speculate that protease IV may be an important contributing factor to the development and propagation of acute lung injury associated with P. aeruginosa via loss of surfactant function within the lung.




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