Altered surfactant protein A gene expression and protein metabolism associated with repeat exposure to inhaled endotoxin

1 Department of Pediatrics, Division of Pediatric Critical Care; 2 Department of Occupational and Environmental Health, College of Public Health; 4 Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52242; and 3 Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina 27710 Submitted 7 March 2003 ; accepted in final form 13 August 2003 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, whereas 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. lipopolysaccharide; collectins; grain dust; environmental exposure Address for reprint requests and other correspondence: C. L. S. George, Dept. of Pediatrics, 200 Hawkins Dr., Univ. of Iowa Hospitals and Clinics, Iowa City, IA 52242 (E-mail: caroline-george{at}uiowa.edu ).