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Am J Physiol Lung Cell Mol Physiol (August 15, 2003). doi:10.1152/ajplung.00064.2003
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Submitted on March 7, 2003
Accepted on August 13, 2003

Altered Surfactant Protein-A Gene Expression and Protein Metabolism Associated with Repeat Exposure to Inhaled Endotoxin

Caroline L.S. George1*, Misty L. White1, Marsha E. O'Neill2, Peter S. Thorne2, David A. Schwartz3, and Jeanne M. Snyder4

1 Division of Pediatrics Critical Care, Department of Pediatrics, University of Iowa, Iowa City, IA, USA
2 Department of Occupational and Environmental Health, University of Iowa, College of Public Health, Iowa City, IA, USA
3 Department of Internal Medicine, Duke University, Durham, NC, USA
4 Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA, USA

* To whom correspondence should be addressed. E-mail: caroline-george{at}uiowa.edu.

Chronically inhaled endotoxin, which is ubiquitous in many occupational and domestic environments, can adversely affect the respiratory system resulting in an inflammatory response and decreased lung function. Surfactant associated protein-A (SP-A) is part of the lung innate immune system and may attenuate the inflammatory response in various types of lung injury. Using a murine model to mimic occupational exposures to endotoxin, we hypothesized that SP-A gene expression and protein would be elevated in response to repeat exposure to inhaled grain dust and to purified lipopolysaccharide(LPS). Our results demonstrate that repeat exposure to inhaled endotoxin, either in the form of grain dust or purified LPS, results in increased whole lung SP-A gene expression and type II alveolar epithelial cell hyperplasia, while SP-A protein levels in lung lavage fluid are decreased. Furthermore, these alterations in SP-A gene activity and protein metabolism are dependent on an intact endotoxin signaling system.




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