OVEREXPRESSION OF GRANULOCYTE-COLONY-STIMULATING FACTOR IN-VIVO DECREASES THE LEVEL OF POLYPLOIDIZATION OF MOUSE BONE-MARROW MEGAKARYOCYTES

The in vivo effect of G-CSF on the maturation of mouse bone marrow meg akaryocytes was studied by monitoring the DNA contents. Megakaryocytes were first identified by a specific 1C2, monoclonal antibody against mouse platelets and megakaryocytes and DNA contents of these cells wer e measured by propidium iodine, Megakaryocytes of mice transgenic for human G-CSF had a modal DNA class of 8N, showing a striking contrast t o the previous reports that normal mouse megakaryocytes from most stra ins have 16N DIVA content as a modal class, Daily 10 mu g administrati on of G-CSF to mice for three to five dag's affected the DNA distribut ion pattern of bone marrow megakaryocytes, with a higher proportion of cells hawing 8N DNA contents, This G-CSF treatment, however, did not influence the peripheral blood platelet count or bone marrow megakaryo cyte number. Administration of G-CSF along with thrombopoietin (TPO) r educed the proportion of megakaryocytes, with 32N DNA, the DNA class t hat was increased by TPO, Finally. the presence of mRNA For the mouse G-CSF receptor was demonstrated in two megakaryoblastic cell lines by reverse transcriptase polymerase chain reaction. These results indicat ed that G-CSF may have a suppressive effect on the maturation of mouse bone marrow megakaryocytes when monitored by the DNA polyploidy. Alth ough further study is clearly necessary, the presence of mRNA for the G-CSF receptor in megakaryocytic lineage strongly suggests the direct action of G-CSF on this cell lineage.