title: Biophysical characterization of the interaction of endotoxins with hemoglobins.
abstract: Bacterial endotoxin (lipopolysaccharide, LPS) is the major component of the outer leaflet of the outer membrane in gram-negative bacteria. During severe infections, bacteria may reach the blood circuit of humans, and endotoxins may be released from the bacteria due to cell division or cell death. In particular enterobacterial forms of LPS represent extremely strong activator molecules of the human immune system causing a rapid induction of cytokine production in monocytes and macrophages. Various mammalian blood proteins have been documented to display LPS binding activities mediating normally decreasing effects in the biological activity of LPS. In more recent studies, the essential systemic oxygen transportation protein hemoglobin (Hb) has been shown to amplify LPS-induced cytokine production on immune cells. The mechanism responsible for this effect is poorly understood. Here, we characterize the interaction of hemoglobin with LPS by using biophysical methods. The data presented, revealing the changes of the type and size of supramolecular aggregates of LPS in the presence of Hb, allow a better understanding of the hemoglobin-induced increase in bioactivity of LPS.
authors.affiliation: Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Howe
authors.forename: Malte
authors.initials: M
authors.lastname: Hammer
authors.forename: Christian
authors.initials: C
authors.lastname: Alexander
authors.forename: Manfred
authors.initials: M
authors.lastname: Rössle
authors.forename: Karin
authors.initials: K
authors.lastname: Fournier
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Mach
authors.forename: Thierry
authors.initials: T
authors.lastname: Waelli
authors.forename: Reginald M
authors.initials: RM
authors.lastname: Gorczynski
authors.forename: Artur J
authors.initials: AJ
authors.lastname: Ulmer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zähringer
authors.forename: Ernst Th
authors.initials: ET
authors.lastname: Rietschel
authors.forename: Klaus
authors.initials: K
authors.lastname: Brandenburg
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002151:Calorimetry; D018360:Crystallography, X-Ray; D016207:Cytokines / Q000097:blood; D004731:Endotoxins / Q000737:chemistry*; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D007834:Lasers; D008050:Lipid A / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry; D008968:Molecular Conformation; D008970:Molecular Weight; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D019779:Salmonella enterica / Q000737:chemistry; D012542:Scattering, Radiation; D012756:Sheep; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D016207:Cytokines; D004731:Endotoxins; D006454:Hemoglobins; D008050:Lipid A; D008070:Lipopolysaccharides