HUVEC co-culture and haematopoietic growth factors modulate human proliferative monocyte activity

Monocytes and macrophages are often claimed to have limited potential for proliferation in vivo and in vitro although a human monocyte subset with increased potential to proliferate in culture, termed the proliferative monocyte (PM), has previously been identified. The response of the putatively less mature PM to conditions conducive to haematopoietic stem cell culture was determined. Co-culture of monocytes on a HUVEC monolayer induced up to four cell divisions in a 9 day period. The PM response to haematopoietic growth factors (Flt3L, SCF, IL-6, IL-3 and M-CSF) was determined. M-CSF induced the greatest proliferative response in PM; IL-3 and Flt3L reduced basal and M-CSF-induced proliferation. The inhibition of M-CSFR kinase activity by GW2580 indicated that the ligand(s) for this receptor was a potent inducer of proliferation of this subset; inhibitors of intracellular signalling pathways also reduced PM proliferation.

► Human monocyte-derived cells proliferate when cultured on a HUVEC monolayer. ► Haematopoietic growth factors (M-CSF, SCF, IL-6, IL-3 and Flt3L) modulate the proliferation of monocyte-derived cells. ► The proliferative response to M-CSF is reduced by the presence of IL-3 and Flt3L. ► Inhibition of M-CSFR kinase activity reduces human monocyte proliferation.