1,25-Dihydroxyvitamin D3 induces normal mononuclear blood cells to differentiate in the direction of monocyte-macrophages

Abstract

Normal blood mononuclear cells incubated in the presence of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in suspension culture showed increased differentiation to adherent macrophages. The effect was specific to 1,25-(OH)2D3 as the closely related metabolite 25-hydroxyvitamin D3 did not increase macrophage numbers. Giant multinuclear cells were observed in increased numbers in 1,25-(OH)2D3-treated cultures. However this effect was not specific to 1,25-(OH)2D3 but due to cell crowding as these cells were also plentiful when cultures without 1,25-(OH)2D3 were incubated at high cell densities. Increased numbers of macrophages were seen after six days of incubation; this effect of 1,25-(OH)2D3 occurred also if the mononuclear cells were depleted of T-cells or exposed to X-irradiation at doses up to 25Gy. Addition of 1,25-(OH)2D3 to cultures in semi-solid media did not, however, increase the numbers of monocyte-macrophage colonies. These results suggest that the target cell for 1,25-(OH)2D3 is of the monocyte-macrophage lineage and is at a relatively late stage of maturation.