The potential of human mast cell progenitors to differentiate into mature mast cells remains after prolonged culture with flt3 ligand, interleukin‐3 or granulocyte‐macrophage colony stimulating factor

Abstract

Summary. Stem cell factor (SCF) plays a key role in the development of mast cells from haemopoietic progenitor cells. In this study we have investigated the effect of the early acting haemopoietic cytokines flt3 ligand (FL), IL-3 and GM-CSF on the SCF-dependent differentiation of mast cells from cord blood mononuclear cells. By using delayed addition of SCF, we examined the potential of mast cell progenitors to keep their capacity to differentiate into mast cells after exposure to factors signalling differentiation into other lineages. Culture with either cytokine for 3 weeks before transfer to SCF-containing medium resulted in the development of mast cells in all cultures. The appearance of mast cells was attenuated when the cells had been in culture with IL-3 or GM-CSF prior to culture in SCF, compared to cultures exposed to SCF alone for 7 weeks. However, a proportion of the cells had not lost the capacity to develop into mast cells. In contrast, in cultures initiated with FL and transferred to medium containing SCF, the same amount of mast cells developed as in the SCF cultures. Thus, cells committed to the mast cell lineage appear to be resistant to the lineage directives of IL-3 and GM-CSF and keep their potential to differentiate into mature mast cells.

Retinoic Acid Inhibits in vitro Development of Mast Cells But Has No Marked Effect on Mature Human Skin Tryptase- and Chymase-Positive Mast Cells

“…Only a low proportion of the cells had di¡erentiated into mast cells, however. We have earlier described that progenitors can survive for at least 3 wk in culture medium in the absence of SCF, and then develop into mast cells when SCF is added (Hjertson et al, 1999). In that study we found that approximately 50 Â 10 3 mast cells developed and that they constituted 30% of the total cells.…”

“…Stem cell factor (SCF), the ligand for Kit, is the most important stimulatory cytokine for human mast cells, inducing the growth and di¡erentiation of mast cells in vitro and in vivo (Irani et al, 1992;Valent et al, 1992;Mitsui et al, 1993;Costa et al, 1996). Other cytokines have been shown to in£uence this process, either by promoting and thrombopoietin] (Saito et al, 1996;Sawai et al, 1999), or by inhibiting [IL-3, IL-4, IL-13, interferon-g, and granulocyte-macrophage colony stimulating factor (GM-CSF)] (Nilsson et al, 1994b;Sillaber et al, 1994;Nilsson and Nilsson, 1995;Du et al, 1997;Kirshenbaum et al, 1998;Hjertson et al, 1999) mast cell development. Some data indicate that uncommitted progenitors and mast cell progenitors have an enhanced susceptibility to inhibitory stimulus compared to more mature cells of the mast cell lineage.…”

KIT signaling is dispensable for human mast cell progenitor development

“…[1][2][3] In fact, prolonged culture with IL-3 inhibits the SCF-induced generation and maturation of mast cells. 40,41 Our findings show that mast cell progenitors, which virtually lack granules, can form granulated pre-mast cells in the absence of SCF and the presence of IL-3 and IL-6. When IL-3 was removed and replaced with SCF, the pre-mast cells rapidly matured.…”

Human mast cells release the migraine-inducing factor pituitary adenylate cyclase-activating polypeptide (PACAP)

“…Human umbilical cord blood-derived mast cells were produced by in vitro differentiation of positively selected cord blood CD34+ progenitor cells (Allcells) as previously described (37,38). Cells were cultured in Serum Free Expansion Media (SFEM Cat.…”