Guanosine-rich oligodeoxynucleotides induce proliferation of macrophage progenitors in cultures of murine bone marrow cells.
Widely used to specifically inhibit gene expression, synthetic oligodeoxynucleotides (ODN) can exert a plethora of non-antisense effects. Immunostimulation by CpG-ODN has attracted particular attention. ODN rich in the nucleotide guanosine (G-rich ODN) constitute another type of sequences displaying non-antisense-mediated effects. We have examined the effects of CpG- and G-rich ODN on primary mouse bone marrow cells (BMC) in vitro. CpG-ODN induced rapid proliferation of B cells and production of IL-6 and IL-12p40. However, when tested in agar colony assays, CpG-ODN failed to promote the formation of colonies. In marked contrast, G-rich non-CpG-ODN led to sustained proliferation of macrophage-like cells without inducing cytokines or hemopoietic growth factors. Unlike CpG-ODN, G-rich ODN effectively induced the formation of macrophage colonies in agar assays, indicating a direct action on progenitor cells. Electrophoretic mobility shift assays revealed specific binding of G-rich ODN to a non-nuclear protein. The ability of a panel of ODN to compete for binding correlated with their potential to induce proliferation of macrophage-like cells from primary mouse BMC. As such, these data reveal a so far unrecognized potential of G-rich ODN to signal directly outgrowth of macrophage progenitors from BMC.
Lang
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Institute of Medical Microbiology, Technical University of Munich, Munich, Germany. immuno.rdi@lrz.tu-muenchen.de
Hültner
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L
Lipford
G B
GB
Wagner
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Heeg
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D000362:Agar; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology; D006151:Guanosine; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology*; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000276:immunology*; D013154:Spleen / Q000166:cytology
D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; D006151:Guanosine; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000362:Agar