The role of haemopoietic cell growth factor (interleukin 3) in the development of haemopoietic cells.

Abstract

Haemopoietic cell development in vivo occurs in restricted sites in association with stromal cells. Haemopoiesis in vitro can be induced in the absence of stromal cells, provided the haemopoietic cells are supplied with appropriate growth stimulatory molecules. Evidence indicates that the same, or functionally similar, growth factors are normally supplied in vivo by the surrounding stromal cells and that the control of haemopoietic cell proliferation and development is regulated locally and is mediated by cell-cell interactions. We have been studying the effects of a growth factor which induces self-renewal and differentiation of multipotential stem cells as well as proliferation and development of lineage-restricted progenitor cells and activation of mature cells. Because of the wide range of activities embraced by this molecule we have termed it haemopoietic cell growth factor (HCGF). It is also known as interleukin 3 and multi-CSF. HCGF allows the survival, proliferation and development of cells and can be used to generate continuously growing, non-leukaemic, factor-dependent cell lines, in vitro (FDC-P). In the absence of HCGF. FDC-P cells die within hours. We have shown that HCGF may exert its primary effects (in terms of cell survival) on ATP generation, via its influence on glucose transport. Studies are also described which indicate that a primary event in differentiation induced by HCGF involves ADP-ribosylation of membrane-associated proteins. The significance of these findings for normal haemopoiesis and in leukaemogenesis is discussed.