title: Galactofuranosyl glycosides: immunomodulatory effects on macrophages and in vivo enhancement of lethality on sepsis.
abstract: Galactofuranoside derivatives were synthesised by the classic Fischer glycosydation method, and their immune modulation properties were studied in vitro and in vivo. NMR spectroscopic and ESI-MS analyses confirmed the purity and authenticity of all derivatives. Their phagocyte capacities were tested in resident macrophages. Methyl β-galactofuranoside (GFB-Me) and n-octyl β-galactofuranoside (GFB-O) had an immune stimulant effect at 25μmolml(-1) with an enhancement of 35.12%±0.06 SD and 17.49%±0.11 SD, respectively, but Methyl α-galactofuranoside (GFA-Me) and n-octyl α-galactofuranoside (GFA-O) gave a low immune response. Methyl α-galactofuranoside 5,6-O-isopropylidene (GFA-IP) and Methyl β-galactofuranoside 5,6-O-isopropylidene (GFB-IP) had negative values relative to the control group of minus 4.96%±0.10 SD and -40.72%±0.07 SD, respectively. Furthermore, GFB-Me and GFB-Me-IP were evaluated in vivo on the lethality induced by cecal ligation and puncture. Cytokine levels and iNOS expression were determined and correlated to mortality data. The results showed that the free HO-5 and HO-6 and the β-configuration are essential for the induction of phagocytic activity by the galactofuranosyl units. The methyl β-galactofuranosides also enhanced lethality during sepsis, increasing the levels of pro-inflammatory cytokines and iNOS expression.
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, PR, Brazil. sassaki@ufpr.br
authors.forename: Guilherme L
authors.initials: GL
authors.lastname: Sassaki
authors.forename: Yanna D
authors.initials: YD
authors.lastname: Rattmann
authors.forename: Arquimedes P
authors.initials: AP
authors.lastname: Santana-Filho
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Riter
authors.forename: Fabíola
authors.initials: F
authors.lastname: Iagher
authors.forename: Edvaldo S
authors.initials: ES
authors.lastname: Trindade
authors.forename: Morgana D
authors.initials: MD
authors.lastname: da Silva
authors.forename: Adair R S
authors.initials: AR
authors.lastname: Santos
authors.forename: Lauro Mera
authors.initials: LM
authors.lastname: de Souza
authors.forename: Marcello
authors.initials: M
authors.lastname: Iacomini
authors.forename: Philip A J
authors.initials: PA
authors.lastname: Gorin
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D006861:Hydrogen Peroxide / Q000378:metabolism; D007082:Ileum / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D018805:Sepsis / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D016207:Cytokines; D006027:Glycosides; D007155:Immunologic Factors; D013481:Superoxides; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II
keywords: Galactofuranosides; Immunomodulation; Inflammation; Sepsis