Stem Cell Factor Can Stimulate the Formation of Eosinophils by Two Types of Murine Eosinophil Progenitor Cells

There are only three known stimuli for eosinophil formation-GM-CSF, interleukin-5 (IL-5), and IL-3. Because mice with inactivation of the gene encoding the common beta receptor chain for GM-CSF, IL-5, and IL-3 (betac(-/-) mice) cannot respond to GM-CSF or IL-5 and do not produce IL-3, they should lack eosinophils. However, they produce reduced numbers of eosinophils, indicating the existence of at least one additional stimulatory factor. Use of betac(-/-) mouse marrow cells failed to detect a novel eosinophil-stimulating factor in cell line- or organ-conditioned media, but stem cell factor (SCF) was found to have a previously unrecognized ability to stimulate the formation of eosinophil colonies or mixed neutrophil-eosinophil colonies. This action of SCF was also observable with marrow cells from other mouse strains and was enhanced by the addition of G-CSF but no other factor tested. Recloning of SCF-stimulated blast colonies showed that progenitors forming pure eosinophil or mixed neutrophil-eosinophil colonies can have a common ancestor but many appear to arise independently from different preprogenitor cells. The observed activity of SCF in marrow cultures was relatively weak, but its action may be stronger in vivo, and SCF needs to be added to GM-CSF, IL-5, and IL-3 in the list of cytokines able to stimulate eosinophil formation.