G-CSF ACCELERATES THE CELL-CYCLING OF HEMATOPOIETIC PROGENITOR CELLS AND ABROGATES THE DECELERATION BY TNF-ALPHA

We examined the effects of granulocyte colony-stimulating factor (G-CS F) on cell-cycling of hematopoietic progenitors in serum-free methylce llulose clonal cultures. Serial observations of the cultures showed ha stening of growth of colonies by G-CSF, as determined by evaluating th e time for individual colonies of 20 cells to reach 40 cells. G-CSF di d not affect the incidence of proliferating cells in each developing c olony. Cell-cycle analysis revealed that addition of G-CSF to cultures led to a decrease in the percentage of cells in the G1 phase of the c ell-cycle, thereby indicating that G-CSF can modulate the cell-cycle o f hematopoietic progenitors mainly by shortening the period of the G1 phase. Tumor necrosis factor alpha (TNF alpha) exerted opposite effect s on cell-cycling of hematopoietic progenitors to those seen with G-CS F. G-CSF abolished the inhibitory effects of TNF alpha on the cell-cyc ling of hematopoietic progenitors. These observations indicate positiv e and negative regulatory roles of C-CSF and TNF alpha, respectively, and their interactions in the regulation of cell-cycling of hematopoie tic progenitors.