Evidence that cell survival is controlled by interleukin-3 independently of cell proliferation

Hemopoietic cell proliferation is controlled by a set of polypeptide growth factors and regulatory molecules that bind to cell surface receptors inducing cellular responses. Maintenance of a viable state, cell growth, DNA synthesis and mitosis are basic properties of proliferating cells, but links between growth factor receptors and each of these cellular outcomes are poorly understood. Most studies have monitored DNA synthesis as a measure of progression through the cell cycle or directly measured viable cell numbers, but cell survival per se as an output of receptor activation by ligand, has received little attention. In this study we have used a bone marrow-derived murine cell line that is dependent on interleukin-3 for growth, to investigate the relationship between DNA synthesis and a biochemical marker of cell survival, reduction of the tetrazolium salt, MTT. We show that at times up to 6 hr, continued DNA synthesis, RNA synthesis, protein synthesis, and mitochondrial respiration are not necessary for background or IL-3-stimulated MTT reduction. Furthermore, dibutyryl cyclic AMP promoted background and IL-3-dependent MTT reduction while simultaneously inhibiting DNA synthesis. These results provide evidence that IL-3 controls events involved in MTT reduction and cell survival independently of DNA synthesis.