Altered surfactant protein A gene expression and protein metabolism associated with repeat exposure to inhaled endotoxin.
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.
George
Caroline L S
CL
Department of Pediatrics, Division of Pediatric Critical Care, University of Iowa, Iowa City, IA 52242, USA. caroline-george@uiowa.edu
White
Misty L
ML
O'Neill
Marsha E
ME
Thorne
Peter S
PS
Schwartz
David A
DA
Snyder
Jeanne M
JM
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002908:Chronic Disease; D004195:Disease Models, Animal; D004391:Dust; D002523:Edible Grain; D015870:Gene Expression / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D016273:Occupational Exposure; D011014:Pneumonia / Q000378:metabolism / Q000503:physiopathology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics* / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics; D020545:Respiratory Mucosa / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors
D004391:Dust; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D037662:Pulmonary Surfactant-Associated Protein A; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors