LPS binding protein is important in the airway response to inhaled endotoxin.
BACKGROUND
Inhaled endotoxin is a risk factor for asthma exacerbation, and endotoxin inhalation by itself recapitulates many of the classical features of asthma in mice, including reversible airflow obstruction and inflammation, airways hyperresponsiveness, and airway remodeling.


OBJECTIVE
Our objective was to determine the importance of LPS binding protein (LBP) in the response to inhaled LPS.


METHODS
We challenged LBP-deficient mice (C57BL/6(LBP-/-)) and C57BL/6 mice with inhaled endotoxin for 4 hours, 5 days, or 4 weeks, followed by 3 days of recovery.


RESULTS
LBP in the lung was significantly increased in LPS-exposed C57BL/6 mice from all 3 groups. Only LPS-exposed C57BL/6 mice had significantly enhanced airway responsiveness to inhaled methacholine. Total lavage cells in LPS-exposed C57BL/6(LBP-/-) mice were significantly reduced compared with those seen in LPS-exposed C57BL/6 mice; however, the percentage of PMNs was similarly increased in both the C57BL/6 and C57BL/6(LBP-/-) mice. TNF-alpha, IL-1 beta, and IL-6 protein concentrations in whole-lung lavage fluid from C57BL/6(LBP-/-) mice were also significantly reduced when compared with those seen in C57BL/6 mice. In C57BL/6(LBP-/-) mice submucosal cell proliferation was significantly reduced in the 1-week group when compared with that seen in similarly exposed C57BL/6 mice. The 4-week exposed C57BL/6 mice had significantly thickened airway submucosa and significantly increased lavaged TGF-beta(1) protein compared with that seen in C57BL/6(LBP-/-) mice.


CONCLUSIONS
These findings indicate that LBP is one of the critical molecules regulating the acute and chronic airway response to inhaled LPS.
Brass
David M
DM
Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, Durham, NC 27710-0001, USA. brass001@mc.duke.edu
Savov
Jordan D
JD
Whitehead
Gregory S
GS
Maxwell
Abby B
AB
Schwartz
David A
DA
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004731:Endotoxins / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D012137:Respiratory System / Q000276:immunology* / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein