Widely used to specifically inhibit gene expression, synthetic oligodeoxynucleotides (ODN)can exert a plethora of non-antisense effects. Immunostimulation by CpG-ODN hasattracted particular attention. ODN rich in the nucleotide guanosine (G-rich ODN) constituteanother type of sequences displaying non-antisense-mediated effects. We have examinedthe 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. How-ever, when tested in agar colony assays, CpG-ODN failed to promote the formation of colo-nies. In marked contrast, G-rich non-CpG-ODN led to sustained proliferation ofmacrophage-like cells without inducing cytokines or hemopoietic growth factors. Unlike CpG-ODN, G-rich ODN effectively induced the formation of macrophage colonies in agarassays, indicating a direct action on progenitor cells. Electrophoretic mobility shift assaysrevealed 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 ofmacrophage-like cells from primary mouse BMC. As such, these data reveal a so far unrec-ognized potential of G-rich ODN to signal directly outgrowth of macrophage progenitorsfrom BMC.
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SchlagwörterGuanosine-rich oligodeoxynucleotides Proliferation Macrophage Bone marrow cell