A novel guanosine analog, 7-thia-8-oxoguanosine, enhances macrophage and lymphocyte antibody-dependent cell-mediated cytotoxicity.
Intraperitoneal treatment of mice with a novel guanosine analog, 7-thia-8-oxoguanosine (7-thia-8-oxoGuo), gives rise to activated splenic lymphocytes and peritoneal macrophages with enhanced capacity to mediate antibody-dependent cellular cytotoxicity (ADCC). ADCC activities against both chicken red blood cells and P815 murine plasmacytoma cells were enhanced, indicating that macrophages as well as lymphocytes functioning as K-cells in the two distinct cytolytic systems, were activated by 7-thia-8-oxoGuo. Furthermore, 7-thia-8-oxoGuo enhanced lymphocyte-mediated ADCC activity in beige (bgJ/bgJ) mice against P815, thus indicating the ability of 7-thia-8-oxoGuo to function as a potent immunomodulator even in an animal that is known to possess selective impairment of naturally occurring killer lymphocytes. These results suggest that 7-thia-8-oxoGuo could serve as an agent for immunomodulation and immunorestoration.
Jin
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A
Department of Immunology, ICN Nucleic Acid Research Institute, Costa Mesa, California 92626.
Mhaskar
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S
Jolley
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WB
Robins
R K
RK
Ojo-Amaize
E A
EA
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects; D008214:Lymphocytes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010954:Plasmacytoma / Q000276:immunology
D000276:Adjuvants, Immunologic; D006151:Guanosine; C061136:isatoribine