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Published ahead of print on February 2, 2006, doi:10.1165/rcmb.2005-0461OC

Am. J. Respir. Cell Mol. Biol., Volume 34, Number 6, June 2006, 704-710

A more recent version of this article appeared on June 1, 2006
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Submitted on December 16, 2005
Revised on February 1, 2006

Surfactant Proteins A and D Enhance Pulmonary Clearance of Pseudomonas aeruginosa

Eric Giannoni1, Teiji Sawa2, Lennell Allen3, Jeanine Wiener-Kronish2, and Sam Hawgood1*

1 Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA; Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA, 2 Department of Anesthesia, University of California San Francisco, San Francisco, CA, USA, 3 Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA

* To whom correspondence should be addressed. E-mail: hawgoods{at}peds.ucsf.edu.

Surfactant protein-A (SP-A) and surfactant protein-D (SP-D), members of the collectin family, are involved in innate host defenses against various bacterial and viral pathogens. In this study, we asked whether SP-A and SP-D enhance clearance of a non-mucoid strain of Pseudomonas aeruginosa from the lungs. We infected mice deficient in SP-A (SP-A-/-), SP-D (SP-D-/-) and both pulmonary collectins (SP-AD-/-) by intratracheal administration of P. aeruginosa. Six hours after infection, bacterial counts were significantly higher in SP-A-/-, SP-D-/- and SP-AD-/- compared to WT mice. Forty eight hours after infection, bacterial counts were significantly higher in SP-A-/- mice compared to WT mice and in SP-AD-/- mice compared to WT, SP-A-/-, and SP-D-/- mice. Phagocytosis of the bacteria by alveolar macrophages was decreased in SP-A-/- and SP-D-/- mice. Levels of MIP-2 and IL-6 were more elevated in the lungs of SP-D and SP-AD-/- mice compared to WT mice. There was more infiltration by neutrophils in the lungs of SP-D-/- compared to both WT and SP-A-/- mice 48 hours after infection. In conclusion, this study shows that both SP-A and SP-D enhance pulmonary clearance of P. aeruginosa by stimulating phagocytosis by AM and by modulating the inflammatory response in the lungs. These findings also show that the functions of SP-A and SP-D are not completely redundant in vivo.




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