title: Lipopolysaccharide-binding protein mediates CD14-independent intercalation of lipopolysaccharide into phospholipid membranes.
abstract: Lipopolysaccharides (LPS, endotoxin) stimulate mononuclear cells to release cytokines which initiate endotoxic effects. Interaction of LPS at low concentrations with target cells is CD14-dependent whereas at high LPS concentrations it is CD14-independent. Here, we demonstrate by resonance energy transfer (RET) technique that nonspecific, CD14-independent intercalation of LPS into membrane systems can be mediated by lipopolysaccharide-binding protein (LBP). It is proposed that in this pathway, LBP breaks down LPS aggregates, transports the smaller units to and inserts them into the phospholipid cell matrix. We furthermore show that LBP also mediates the intercalation of other negatively charged amphiphilic molecules. We propose a model explaining CD14-independent cell activation at high endotoxin concentrations.
authors.affiliation: Research Center Borstel, Center for Medicine and Biosciences, Germany.
authors.forename: A B
authors.initials: AB
authors.lastname: Schromm
authors.forename: K
authors.initials: K
authors.lastname: Brandenburg
authors.forename: E T
authors.initials: ET
authors.lastname: Rietschel
authors.forename: H D
authors.initials: HD
authors.lastname: Flad
authors.forename: S F
authors.initials: SF
authors.lastname: Carroll
authors.forename: U
authors.initials: U
authors.lastname: Seydel
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008562:Membrane Glycoproteins; D008563:Membrane Lipids / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D008563:Membrane Lipids; D010743:Phospholipids; D000099231:Lipopolysaccharide-Binding Protein