Guanosine-rich oligodeoxynucleotides induce proliferation of macrophage progenitors in cultures of murine bone marrow cells

Widely used to specifically inhibit gene expression, synthetic oligodeoxynu cleotides (ODN) can exert a plethora of non-antisense effects. Immunostimul ation by CpG-ODN has attracted particular attention. ODN rich in the nucleo tide 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 induce d rapid proliferation of B cells and production of IL-6 and IL-12p40. Howev er, when tested in agar colony assays, CpG-ODN failed to promote the format ion of colonies. In marked contrast, G-rich non-CpG-ODN led to sustained pr oliferation of macrophage-like cells without inducing cytokines or hemopoie tic growth factors. Unlike CpG-ODN, G-rich ODN effectively induced the form ation of macrophage colonies in agar assays, indicating a direct action on progenitor cells. Electrophoretic mobility shift assays revealed specific b inding of G-rich ODN to a non-nuclear protein. The ability of a panel of OD N to compete for binding correlated with their potential to induce prolifer ation 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 out growth of macrophage progenitors from BMC.