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 monocytes. IFI 16 and a related mouse protein, p202, control cellular proliferation by binding and modulating the functions of cell cycle regulatory factors including p53 and the retinoblastoma gene product, pRb. In this study, we examined IFI 16 expression in myeloid precursor cells cultured in vitro in colony-forming assays using granulocyte (G-) and granulocyte-macrophage (GM-) colony-stimulating factor (CSF). IFI 16 was expressed in 100% of CD34+ cells isolated from human bone marrow. When the CD34+ cells were induced to differentiate, two sub-populations of cells were identified by two-color cytofluorography: the CD14+ (monocytoid) cells all expressed IFI 16, whereas the CD14- (polymorphonuclear precursor) cells did not. The strongest expression of IFI 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 independent colony-forming assays, the number of IFI 16+ cells correlated closely with the numbers of monocyte precursors identified morphologically (R2 = 0.99), but was unrelated to the numbers of myelocytes, promyelocytes, and metamyelocytes; nor was IFI 16 expressed by erythroid or eosinophil precursors. We conclude that IFI 16 is expressed in CD34+ and monocytoid daughter cells, but is rapidly and markedly down-regulated at the corresponding stages of polymorphonuclear and erythroid development. This differential expression of IFI 16 in myeloid precursor subpopulations and its perceived molecular properties are consistent with a possible role in regulating myelopoiesis.
Cellular Cytotoxicity Laboratory, The Austin Research Institute, Heidelberg, Australia.
M J
MJ
Dawson
N J
NJ
Elwood
R W
RW
Johnstone
J A
JA
Trapani
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D051379:Mice; D009000:Monocytes / Q000145:classification / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics
D015703:Antigens, CD; D018952:Antigens, CD34; C489664:Ifi16 protein, mouse; D018950:Lipopolysaccharide Receptors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D016179:Granulocyte Colony-Stimulating Factor; C076700:IFI16 protein, human; D016178:Granulocyte-Macrophage Colony-Stimulating Factor