THE IFN-INDUCIBLE NUCLEOPROTEIN IFI-16 IS EXPRESSED IN CELLS OF THE MONOCYTE LINEAGE, BUT IS RAPIDLY AND MARKEDLY DOWN-REGULATED IN OTHER MYELOID PRECURSOR POPULATIONS

IFI 16 is an interferon-inducible nucleoprotein expressed by human mon ocytes, IFI 16 and a related mouse protein, p202, control cellular pro liferation by binding and modulating the functions of cell cycle regul atory factors including p53 and the retinoblastoma gene product, pRb, In this study, we examined IFI 16 expression in myeloid precursor cell s cultured in vitro in colony-forming assays using granulocyte (G-) an d granulocyte-macrophage (GM-) colony-stimulating factor (CSF), IFI 16 was expressed in 100% of CD34(+) cells isolated from human bone marro w. When the CD34(+) cells were induced to differentiate, two sub-popul ations of cells were identified by two-color cytofluorography: the CD1 4(+) (monocytoid) cells all expressed IFI 16, whereas the CD14(-) (pol ymorphonuclear precursor) cells did not. The strongest expression of I FI 16 was in the cells staining brightest for CD14, whereas depletion of CD14(+) monocytoid cells from mixed monocytic/granulocytic cultures largely abolished IFI 16-stained cells. Furthermore, in eight indepen dent colony-forming assays, the number of IFI 16(+) cells correlated c losely with the numbers of monocyte precursors identified morphologica lly (R-2 = 0.99), but was unrelated to the numbers of myelocytes, prom yelocytes, and metamyelocytes; nor was IFI 16 expressed by erythroid o r eosinophil precursors, We conclude that IFI 16 is expressed in CD34( +) and monocytoid daughter cells, but is rapidly and markedly do down- regulated at the corresponding stages of polymorphonuclear and erythro id development. This differential expression of IFI 16 in myeloid prec ursor subpopulations and its perceived molecular properties are consis tent with a possible role in regulating myelopoiesis.