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 megakaryocytes 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 were measured by propidium iodine, Megakaryocytes of mice transgenic for human G-CSF had a modal DNA class of 8N, showing a striking contrast to the previous reports that normal mouse megakaryocytes from most strains have 16N DIVA content as a modal class, Daily 10 mu g administration of G-CSF to mice for three to five dag's affected the DNA distribution 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 megakaryocyte number. Administration of G-CSF along with thrombopoietin (TPO) reduced the proportion of megakaryocytes, with 32N DNA, the DNA class that 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 indicated that G-CSF may have a suppressive effect on the maturation of mouse bone marrow megakaryocytes when monitored by the DNA polyploidy. Although 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.