title: Activation of the respiratory burst in murine phagocytes by certain guanine ribonucleosides modified at the 7 and 8 positions: possible involvement of a pertussis toxin-sensitive G-protein.
abstract: The capacity of certain guanine ribonucleosides (modified at the 7 and/or 8 positions) to enhance the respiratory burst of murine peritoneal phagocytes was evaluated. The results show that 8-mercaptoguanosine, 8-bromoguanosine, 7-methyl-8-oxoguanosine and 7-thia-8-oxoguanosine, when injected intraperitoneally into mice, induced peritoneal phagocytes to generate reactive oxygen species as early as 1 h after injection. In vivo administration of the nucleosides induced higher levels of phagocyte activation than in vitro treatment with the same nucleosides. However, the addition of interferon alpha/beta in vitro significantly increased the magnitude of phagocyte activation by the nucleosides, suggesting an important role for cytokines/lymphokines in the nucleoside-induced phagocyte activation in vivo. Furthermore, pre-treatment of phagocytes in vitro with Bordetella pertussis toxin, before treatment with the guanosines, inhibited their capacity to induce the respiratory burst. These observations establish these low-molecular-weight compounds as interesting probes for the study of stimulus-response coupling in phagocytes.
authors.affiliation: ICN Nucleic Acid Research Institute, Costa Mesa, CA 92626.
authors.forename: E A
authors.initials: EA
authors.lastname: Ojo-Amaize
authors.forename: B
authors.initials: B
authors.lastname: Rubalcava
authors.forename: T L
authors.initials: TL
authors.lastname: Avery
authors.forename: H B
authors.initials: HB
authors.lastname: Cottam
authors.forename: S S
authors.initials: SS
authors.lastname: Matsumoto
authors.forename: W B
authors.initials: WB
authors.lastname: Jolley
authors.forename: R K
authors.initials: RK
authors.lastname: Robins
mesh_terms: D000818:Animals; D019204:GTP-Binding Proteins / Q000502:physiology*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008163:Luminescent Measurements; D008165:Luminol; D051379:Mice; D008808:Mice, Inbred CBA; D010101:Oxygen Consumption / Q000187:drug effects; D010529:Peritoneal Cavity / Q000166:cytology; D037342:Pertussis Toxin; D010586:Phagocytes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013864:Thioglycolates; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
chemical_list: D013864:Thioglycolates; D010566:Virulence Factors, Bordetella; D006151:Guanosine; C035169:8-bromoguanosine; D008165:Luminol; D015054:Zymosan; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate