title: Analysis of interaction of cloned human and/or sheep fetal hemoglobin gamma-chain and LPS in augmenting induction of inflammatory cytokine production in vivo and in vitro.
abstract: We have reported earlier that purified preparations of sheep fetal hemoglobin, but not adult hemoglobin, in concert with non-stimulatory doses of lipopolysaccharide (LPS) (lipid A), act cooperatively to regulate in vitro production of a number of cytokines, including TNFalpha, TGFbeta and IL-6 from murine and human leukocytes. Following in vivo treatment of mice with the same combination of hemoglobin and LPS, harvested spleen or peritoneal cells showed a similar augmented capacity to release these cytokines into culture supernatants. We report below that genetically cloned gamma-chain of human or sheep fetal hemoglobin, but not cloned alpha- or beta-chains, can produce this cooperative effect, as indeed can HPLC purified, heme-free, gamma-chains derived from cord blood fetal hemoglobin, and that purified haptoglobin completely abolishes the cooperative interaction.
authors.affiliation: Departments of Surgery, University Health Network, Toronto, Ontario, Canada.
authors.forename: R M
authors.initials: RM
authors.lastname: Gorczynski
authors.forename: C
authors.initials: C
authors.lastname: Alexander
authors.forename: W
authors.initials: W
authors.lastname: Bessler
authors.forename: K
authors.initials: K
authors.lastname: Fournier
authors.forename: P
authors.initials: P
authors.lastname: Hoffmann
authors.forename: J P
authors.initials: JP
authors.lastname: Mach
authors.forename: E Th
authors.initials: ET
authors.lastname: Rietschel
authors.forename: L
authors.initials: L
authors.lastname: Song
authors.forename: Th
authors.initials: T
authors.lastname: Waelli
authors.forename: O
authors.initials: O
authors.lastname: Westphal
authors.forename: U
authors.initials: U
authors.lastname: Zahringer
authors.forename: I
authors.initials: I
authors.lastname: Khatri
mesh_terms: D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005319:Fetal Hemoglobin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D005914:Globins / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*; D006242:Haptoglobins / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008050:Lipid A / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects*; D051379:Mice; D008969:Molecular Sequence Data; D012756:Sheep; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D006242:Haptoglobins; D015850:Interleukin-6; D008050:Lipid A; D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D005914:Globins; D005319:Fetal Hemoglobin