Substituted guanine ribonucleosides as B cell activators.
Monosubstituted (at C8) and disubstituted (at C8 and N7) guanine ribonucleosides activate human and murine B lymphocytes. A newly developed disubstituted analog, 7-allyl 8-oxoguanosine (7ally18oGuo), in a dose-dependent manner induced anti-tetanus-specific IgG antibody response in peripheral blood mononuclear cells in humans. In addition, 7ally18oGuo activated monocytes from healthy subjects and patients with common variable immunodeficiency to produce interleukin 1. Furthermore, 7ally18oGuo induced changes in plasma membrane potentials and intracellular pH in human peripheral blood mononuclear cells. The role of monosubstituted and disubstituted compounds in restoring immunodeficient states in mice and humans, both in vivo and in vitro, is reviewed.
Division of Basic and Clinical Immunology, University of California, Irvine 92717.
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S
Gupta
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B
Vayuvegula
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S
Gollapudi
D001402:B-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007074:Immunoglobulin G / Q000096:biosynthesis; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D013745:Tetanus Toxoid / Q000494:pharmacology
D007074:Immunoglobulin G; D007375:Interleukin-1; D013745:Tetanus Toxoid; D006151:Guanosine; C068562:loxoribine