EVIDENCE THAT CELL-SURVIVAL IS CONTROLLED BY INTERLEUKIN-3 INDEPENDENTLY OF CELL-PROLIFERATION

Hemopoietic cell proliferation is controlled by a set of polypeptide g rowth factors and regulatory molecules that bind to cell surface recep tors inducing cellular responses. Maintenance of a viable state, cell growth, DNA synthesis and mitosis are basic properties of proliferatin g cells, but links between growth factor receptors and each of these e el lu lar outcomes are poorly understood. Most studies have monitored DNA synthesis as a measure oi progression through the cell cycle or di rectly measured viable cell numbers, but cell survival per se as an ou tput 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 relation ship 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 mit ochondrial respiration are not necessary for background or IL-3-stimul ated MTT reduction. Furthermore, dibutyryl cyclic AMP promoted backgro und and IL-3-dependent MTT reduction while simultaneously inhibiting D NA synthesis. These results provide evidence that IL-3 controls events involved in MTT reduction and cell survival independently of DNA synt hesis. (C) 1995 Wiley-Liss, Inc.