Insulin-like growth factor-I inhibits apoptosis in IL-3-dependent hemopoietic cells.

The death of hemopoietic cells on withdrawal of CSF occurs by a mechanism known as apoptosis characterized by the early degradation of chromatin into oligonucleosome-length fragments. Insulin-like growth factor I plays a pivotal role in the regulation of somatic cell growth as a mediator of growth hormone action. Animals with low levels of circulating IGF-I are more vulnerable to infections and have diminished immune responses. To analyze the possibility of a regulatory role of IGF-I on hemopoiesis and determine its mechanism of action, we have studied the effect of this growth factor on the survival and proliferation of two IL-3-dependent hemopoietic cell lines and in IL-3-responsive primary cultures of bone marrow-derived mast cells. In IL-3-depleted cultures, IGF-I prevented DNA fragmentation and apoptotic cell death. Insulin at high concentration had a weak protective action and IGF-II was inactive in suppressing apoptosis in these IL-3-dependent hemopoietic cells. Cell proliferation was also stimulated by IGF-I in the absence of other hemopoietic growth factors although it was a weak mitogen when compared with IL-3. These results indicate that circulating or locally produced IGF-I may promote survival of both the steady state hemopoietic precursor population and cytokine-producing cells and could therefore regulate hemopoiesis acting in a concerted manner with other CSF.