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.
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.
Ojo-Amaize
E A
EA
ICN Nucleic Acid Research Institute, Costa Mesa, CA 92626.
Rubalcava
B
B
Avery
T L
TL
Cottam
H B
HB
Matsumoto
S S
SS
Jolley
W B
WB
Robins
R K
RK
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
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