title: Evidence of a trimolecular complex involving LPS, LPS binding protein and soluble CD14 as an effector of LPS response.
abstract: The kinetics of the interaction of lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP) and CD14 was studied using surface plasmon resonance. The association and dissociation rate constants for the binding of LPS and rsCD14 were 2.9 x 10(4) M(-1) s(-1) and 0.07 s(-1) respectively, yielding a binding constant of 4.2 x 10(5) M(-1). Significantly, the presence of LBP increased not only the association rate but also the association constant for the interaction between LPS and CD14 by three orders of magnitude. Our experimental results suggest that LBP interacts with LPS and CD14 to form a stable trimolecular complex that has significant functional implications as it allows monocytes to detect the presence of LPS at a concentration as low as 10 pg/ml or 2 pM, and to respond by secreting interleukin-6. Thus, LBP is not merely transferring LPS to CD14 but it forms an integral part of the LPS-rLBP-rsCD14 complex.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
authors.forename: Celestine J
authors.initials: CJ
authors.lastname: Thomas
authors.forename: Mili
authors.initials: M
authors.lastname: Kapoor
authors.forename: Shilpi
authors.initials: S
authors.lastname: Sharma
authors.forename: Huguette
authors.initials: H
authors.lastname: Bausinger
authors.forename: Umit
authors.initials: U
authors.lastname: Zyilan
authors.forename: Dan
authors.initials: D
authors.lastname: Lipsker
authors.forename: Daniel
authors.initials: D
authors.lastname: Hanau
authors.forename: Avadhesha
authors.initials: A
authors.lastname: Surolia
mesh_terms: D000209:Acute-Phase Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015850:Interleukin-6 / Q000096:biosynthesis; D007700:Kinetics; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology*; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D020349:Surface Plasmon Resonance; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D000099231:Lipopolysaccharide-Binding Protein