title: Inhibition of LPS-induced activation of alveolar macrophages by high concentrations of LPS-binding protein.
abstract: Lipopolysaccharide (LPS)-binding protein regulates the effects of LPS on immunocompetent cells. By catalyzing the binding of LPS to membrane CD14, LPS-binding protein (LBP) potentiates both the inflammatory response and internalization of LPS. LBP-mediated transport of LPS into high density lipoprotein particles participates in LPS clearance. Elevated serum levels of LBP have been shown to elicit protective effects in vivo. Because the expression of LBP is upregulated in lung epithelial cells upon proinflammatory stimulation, we here investigated whether LBP modulates inflammatory responses by lung specific cells. The moderate elevation of LBP concentrations enhanced both LPS-induced signaling and LPS uptake by rat alveolar macrophages, whereas strongly elevated LBP levels inhibited both. In contrast, the lung epithelial cell line A549 responded to high concentrations of LBP by an enhanced LPS uptake which did not result in cellular activation, suggesting an anti-inflammatory function of these cells by clearing LPS.
authors.affiliation: Department of Immunology and Cell Biology, Center for Medicine and Bioscience, Borstel, Germany. lutz.hamann@charite.de
authors.forename: Lutz
authors.initials: L
authors.lastname: Hamann
authors.forename: Cordula
authors.initials: C
authors.lastname: Stamme
authors.forename: Artur J
authors.initials: AJ
authors.lastname: Ulmer
authors.forename: Ralf R
authors.initials: RR
authors.lastname: Schumann
mesh_terms: D000209:Acute-Phase Proteins; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004705:Endocytosis; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein