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-alpha, 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.
Suzuki
Hirohito
H
The Second Department of Internal Medicine, Mie University School of Medicine, Mie, Japan.
Katayama
Naoyuki
N
Ikuta
Yasushi
Y
Mukai
Katsumi
K
Fujieda
Atsushi
A
Mitani
Hidetsugu
H
Araki
Hiroto
H
Miyashita
Hiroyuki
H
Hoshino
Natsuki
N
Nishikawa
Hiroyoshi
H
Nishii
Kazuhiro
K
Minami
Nobuyuki
N
Shiku
Hiroshi
H
D000818:Animals; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016895:Culture Media, Serum-Free; D007377:Interleukin-3; D018950:Lipopolysaccharide Receptors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor