Further study of internal autocrine regulation of multipotent hematopoietic cells.

We have extended the study of the effects of antisense oligodeoxynucleotides on hematopoietic colony formation to include the effects of antisense to granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF) on bone marrow cultures. GM-CSF antisense and GM-CSF receptor antisense cause an increase in mixed erythroid:nonerythroid colonies and a decrease in mixed nonerythroid colonies, which is an effect opposite to that described previously for erythropoietin (Epo) and Epo receptor antisense. The effect of GM-CSF antisense oligomer is not abrogated by the presence of the ligand in the culture. Antisense oligomers to G-CSF and M-CSF have no effect. When Epo and GM-CSF antisense oligomers are added simultaneously, the effects seem to be independent, with the GM-CSF antisense predominating. These data support the hypothesis of internal autocrine regulation of multipotent hematopoietic precursor cells, and extend the concept to myeloid as well as erythroid differentiation.