Activities of granulocyte‐macrophage colony‐stimulating factor and interleukin‐3 on monocytes

We examined the actions of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and interleukin‐3 (IL‐3) on human monocytes, using a serum‐free culture system. GM‐CSF and IL‐3 did not promote the differentiation of monocytes into macrophages but rather into cells with a phenotype compatible with that of immature dendritic cells (DCs). The addition of fetal bovine serum to serum‐free cultures with GM‐CSF or IL‐3 restored the differentiation of monocytes into macrophages. Cells generated with GM‐CSF or IL‐3 elicited phagocytic activity. Cells generated in the presence of GM‐CSF or IL‐3, followed by the addition of tumor necrosis factor‐α, displayed a phenotype of mature DCs, and primed and stimulated immunogenic peptide‐specific T lymphocytes. Surprisingly, GM‐CSF and IL‐3 inhibited macrophage colony‐stimulating factor (M‐CSF)‐dependent differentiation of monocytes into macrophages and induced differentiation into immature DCs. We asked if the inhibition of M‐CSF‐dependent differentiation into macrophages by GM‐CSF or IL‐3 was associated with the expression of M‐CSF receptors (M‐CSFR). GM‐CSF or IL‐3 down‐regulated the expression of M‐CSFR. These data demonstrate that GM‐CSF and IL‐3 primarily support the differentiation of monocytes into DCs and inhibit M‐CSF‐dependent differentiation into macrophages by suppressing the expression of M‐CSFR, thereby promoting differentiation into DCs. Am. J. Hematol. 75:179–189, 2004. © 2004 Wiley‐Liss, Inc.