Asthma and endotoxin: lipopolysaccharide-binding protein and soluble CD14 in bronchoalveolar compartment.
In allergic asthma, inhalation of antigen provokes an early increase in microvascular permeability with protein extravasation and a delayed recruitment of inflammatory cells. We showed that similar concentrations of lipopolysaccharide (LPS) are present in bronchoalveolar lavage fluid (BALF) in 12 subjects without asthma (86.5 +/- 53.8 pg/ml) and 12 subjects with mild asthma (111 +/- 37.0 pg/ml). These LPS levels are insufficient to stimulate cytokine release without accessory molecules. BALF obtained 24 h after segmental ragweed antigen challenge in 11 asthmatics allergic to ragweed contained increased levels of two LPS accessory molecules compared with preantigen BALF, 158-fold more LPS-binding protein (LBP) 4.83 +/- 2.02 vs. 742 +/- 387 ng/ml; P < 0.03) and 31.6-fold more soluble CD14 (sCD14) (3.45 +/- 1.04 vs. 110 +/- 51.6 ng/ml; P < 0.02). Postantigen BALF enhanced binding of fluorescein-conjugated LPS to CD14-bearing THP-1 cells and supported LPS-induced non-CD14-bearing endothelial cell expression of intercellular adhesion molecule-1 and interleukin-6, indicating functional LBP and sCD14. We suggest that extravasation of LBP and sCD14 into the bronchoalveolar compartment after antigen inhalation may enhance the capacity of inhaled or aspirated LPS to activate an inflammatory cascade that may amplify the inflammatory response to inhaled antigen in some asthmatics.
Dubin
W
W
Department of Medicine, University of Maryland Medical School, Baltimore 21201, USA.
Martin
T R
TR
Swoveland
P
P
Leturcq
D J
DJ
Moriarty
A M
AM
Tobias
P S
PS
Bleecker
E R
ER
Goldblum
S E
SE
Hasday
J D
JD
D000209:Acute-Phase Proteins; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D002352:Carrier Proteins / Q000032:analysis*; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D008562:Membrane Glycoproteins; D009994:Osmolar Concentration; D010940:Plant Proteins / Q000276:immunology; D012016:Reference Values; D012995:Solubility; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D000941:Antigens; D002352:Carrier Proteins; D004731:Endotoxins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D010940:Plant Proteins; D000099231:Lipopolysaccharide-Binding Protein