title: Enhancing actions of peptides derived from the γ-chain of fetal human hemoglobin on the immunostimulant activities of monophosphoryl lipid A.
abstract: Hemoglobin and its structures have been described since the 1990s to enhance a variety of biological activities of endotoxins (LPS) in a dose-dependent manner. To investigate the interaction processes in more detail, the system was extended by studying the interactions of newly designed peptides from the γ-chain of human hemoglobin with the adjuvant monophosphoryl lipid A (MPLA), a partial structure of lipid A lacking its 1-phosphate. It was found that some selected Hbg peptides, in particular two synthetic substructures designated Hbg32 and Hbg35, considerably increased the bioactivity of MPLA, which alone was only a weak activator of immune cells. These findings hold true for human mononuclar cells, monocytes and T lymphocytes. To understand the mechanisms of action in more detail, biophysical techniques were applied. These showed a peptide-induced change of the MPLA aggregate structure from multilamellar into a non-lamellar, probably inverted, cubic structure. Concomitantly, the peptides incorporated into the tightly packed MPLA aggregates into smaller units down to monomers. The fragmentation of the aggregates was an endothermic process, differing from a complex formation but rather typical for a catalytic reaction.
authors.affiliation: Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany ajulmer@fz-borstel.de kbrandenburg@fz-borstel.de.
authors.forename: Artur J
authors.initials: AJ
authors.lastname: Ulmer
authors.affiliation: Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany.
authors.forename: Yani
authors.initials: Y
authors.lastname: Kaconis
authors.affiliation: Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Heinbockel
authors.affiliation: Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany.
authors.forename: Wilmar
authors.initials: W
authors.lastname: Correa
authors.affiliation: Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Alexander
authors.affiliation: Berlin Institute of Health, Berlin, Germany.
authors.forename: Ernst Th
authors.initials: ET
authors.lastname: Rietschel
authors.affiliation: Institute de Biochemie, University de Lausanne, Lausanne, Switzerland.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Mach
authors.affiliation: Department of Surgery and Immunology, University Health Network, Toronto, Canada.
authors.forename: Reginald M
authors.initials: RM
authors.lastname: Gorczynski
authors.affiliation: Clinique La Prairie, Clarens, Switzerland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Heini
authors.affiliation: European Molecular Biology Laboratory, Hamburg outstation, Hamburg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Rössle
authors.affiliation: Friedrich-Schiller-Universität Jena, Elektronenmikroskopisches Zentrum, Jena, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Richter
authors.affiliation: Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gutsmann
authors.affiliation: Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brandenburg
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005326:Fetal Proteins / Q000378:metabolism*; D006454:Hemoglobins / Q000138:chemical synthesis / Q000378:metabolism*; D006801:Humans; D007114:Immunization; D008050:Lipid A / Q000031:analogs & derivatives* / Q000378:metabolism; D008968:Molecular Conformation; D009000:Monocytes / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D005326:Fetal Proteins; D006454:Hemoglobins; D008050:Lipid A; D010455:Peptides; C048436:monophosphoryl lipid A
keywords: Lipopolysaccharide; cytokine induction; monophosphoryl lipid A; γ-chain of human hemoglobin