title: Biophysical investigations into the interactions of endotoxins with bile acids.
abstract: The interaction of selected endotoxin preparations (lipid A from Erwinia carotovora and LPS Re and Ra from Salmonella enterica sv. Minnesota strains R595 and R60, respectively) with selected bile acids was investigated biophysically. Endotoxin aggregates were analyzed for their gel-to-liquid crystalline phase behavior, the type of their aggregates, the conformation of particular functional groups, and their Zeta potential in the absence and presence of the bile acids by applying Fourier-transform infrared spectroscopy, differential scanning calorimetry, measurements of the electrophoretic mobility, and synchrotron radiation X-ray scattering. In addition, the ability of the endotoxins to induce cytokines in human mononuclear cells was tested in the absence and presence of varying concentrations of bile acids. The data show that the endotoxin:bile acid interaction is not governed by Coulomb forces, rather a hydrophobic interaction takes place. This leads to an enhanced formation of the inherent cubic aggregate structures of the endotoxins, concomitant with a slight disaggregation, as evidenced by freeze-fracture electron microscopy. Parallel to this, the addition of bile acids increased the bioactivity of lipid A and, to a lower degree, also that of the tested rough mutant LPS at lower concentrations of the endotoxin preparation, a finding similar as reported for the interaction of other agents such as hemoglobin. These data imply that there are general mechanisms that govern the expression of biological activities of endotoxins.
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuoka
authors.forename: Walter
authors.initials: W
authors.lastname: Richter
authors.forename: Jörg
authors.initials: J
authors.lastname: Howe
authors.forename: Jörg
authors.initials: J
authors.lastname: Andrä
authors.forename: Manfred
authors.initials: M
authors.lastname: Rössle
authors.forename: Christian
authors.initials: C
authors.lastname: Alexander
authors.forename: Thomas
authors.initials: T
authors.lastname: Gutsmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Brandenburg
mesh_terms: D001647:Bile Acids and Salts / Q000737:chemistry*; D001703:Biophysics; D002152:Calorimetry, Differential Scanning; D002635:Chenodeoxycholic Acid / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis; D003685:Dehydrocholic Acid / Q000737:chemistry; D003840:Deoxycholic Acid / Q000737:chemistry; D004563:Electrochemistry; D004731:Endotoxins / Q000737:chemistry*; D005614:Freeze Fracturing; D006801:Humans; D066298:In Vitro Techniques; D008050:Lipid A / Q000494:pharmacology; D008095:Lithocholic Acid / Q000737:chemistry; D009000:Monocytes / Q000378:metabolism; D016973:Pectobacterium carotovorum / Q000737:chemistry; D019779:Salmonella enterica / Q000737:chemistry; D020358:Sodium Cholate / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D001647:Bile Acids and Salts; D016207:Cytokines; D004731:Endotoxins; D008050:Lipid A; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D008095:Lithocholic Acid; D003685:Dehydrocholic Acid; D020358:Sodium Cholate