Granulocyte-macrophage colony-stimulating factor antagonizes the transforming growth factor-beta-induced expression of Fc gamma RIII (CD16) on human monocytes.
Fc-gamma receptor III (Fc gamma RIII, CD16) type A is expressed on natural killer cells, on a small subset of peripheral blood monocytes and on mature macrophages. Along with differentiation into macrophages, monocytes will express Fc gamma RIII when cultured with transforming growth factor-beta (TGF-beta). In view of the involvement of granulocyte-macrophage colony-stimulating factor (GM-CSF) in myeloid cell differentiation, we investigated the effect of this cytokine on Fc gamma RIII expression in cultures of peripheral blood monocytes. GM-CSF antagonized TGF-beta-induced expression of Fc gamma RIII on monocytes in vitro in a dose-dependent way. The effect of GM-CSF persisted in cultures until at least day 7. The suppression was at the mRNA level, as shown by Northern analyses with a CD16 specific probe, and the signalling pathway involved tyrosine kinase activity. Interferon-gamma and interleukin-2 had no effect on the induced expression of Fc gamma RIII by TGF-beta, while interleukin-4, similar to GM-CSF, antagonized this induction. Our findings suggest that regulatory cytokine networks can drive monocytes into different effector functions and differentiation pathways.
Kruger
M
M
Department of Pathophysiology, Catholic University of Leuven, Belgium.
Coorevits
L
L
De Wit
T P
TP
Casteels-Van Daele
M
M
Van De Winkel
J G
JG
Ceuppens
J L
JL
D016227:Benzoquinones; D015152:Blotting, Northern; D018929:Cell Culture Techniques; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D047029:Lactams, Macrocyclic; D009000:Monocytes / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000276:immunology
D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D011809:Quinones; D012333:RNA, Messenger; D017452:Receptors, IgG; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D017828:Rifabutin; C020754:herbimycin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases