Interleukin 3 and cell cycle progression

Abstract

Interleukin 3 (IL-3) is a regulatory glycoprotein required for the proliferation and differentiation of cells from many if not all hemopoietic lineages. With the emergence of the competence-progression model of cell proliferation, which predicts that growth factors function at specific stages of the cell cycle, we examined the possibility that IL-3 functions at a specific stage of the cell cycle. C-63 cells were developed as a cell line from normal murine bone marrow. They have a mast cell phenotype and require pokeweed-stimulated spleen cell-conditioned medium (CM), a rich source of IL-3, for their continued growth. Exponentially growing cells were transferred from growth medium, which contains CM, to medium lacking CM or IL-3. After 24 hours, cell viability had decreased 40-50%. The remaining viable cells did not incorporate 3H-thymidine, and displayed a single peak at G1 in a DNA histogram. Restimulation of these cells with CM or IL-3 resulted in a dramatic rise in 3H-thymidine uptake 20-24 hours after restimulation. DNA histograms of restimulated cultures indicated that the cells were progressing in a wave-like fashion throughout the remainder of the cell cycle. The length of time necessary for cells to be in contact with CM or IL-3 before they could progress into the remainder of the cell cycle was also examined. Cells incubated with CM or IL-3 for less than 16 hours could not progress into S phase, whereas cells incubated for 16 hours or longer could progress into S phase and through the remainder of the cell cycle. These data suggest that IL-3 exerts its function at a specific stage of the cell cycle.