COMPLEMENTARY AND ANTAGONISTIC EFFECTS OF IL-3 IN THE EARLY DEVELOPMENT OF HUMAN MEGAKARYOCYTES IN CULTURE

The effect of IL-3 on the early steps in the growth and development of megakaryocytes (MX) in culture has been studied. Although thrombopoie tin (TPO) by itself could support the development of mature CD41(+) MX from pre-MK, the number of cells produced was greatly augmented by th e addition of IL-3 and SCF. IL-3 was also able to support the growth o f MK colonies in semi-solid media (CFU-MK). The CD41(+) cells that dev eloped in suspension cultures containing IL-3 differed phenotypically from those that developed without this agent. Cells grown in the prese nce of IL-3 lost CD34 expression more rapidly, expressed lower levels of the platelet glycoproteins gpIIb-IIIa and Ib and achieved lower deg rees of polyploidy than in the absence of IL-3. The inhibitory effects of IL-3 were not a consequence of the dilution of the mature cells by increased numbers of immature cells since it was observed under condi tions in which IL-3 did not stimulate MK growth. The results obtained in these cultures suggest that IL-3 plays an important role in early M K development, but inhibits further maturation after endoreduplication begins. Thus, prolonged contact with IL-3 results in the appearance o f cells that do not mature normally.