Regulation of IFN-gamma-receptor expression in human monocytes by granulocyte-macrophage colony-stimulating factor.
The regulation of human IFN-gamma receptor (IFN-gamma-R) expression by granulocyte-macrophage CSF (GM-CSF) was investigated. On monocytic cell lines (U937, HL60) and peripheral blood monocytes, IFN-gamma-binding capacity was down-regulated upon incubation with GM-CSF. Scatchard plot analyses revealed that down-regulation was caused by a decrease in IFN-gamma-R number rather than by a change in affinity. GM-CSF treatment did not reduce IFN-gamma-R-specific mRNA levels, but reduced the half-life of membrane-expressed IFN-gamma-R, indicating a post-translational control of IFN-gamma-R by GM-CSF. Because both IFN-gamma and GM-CSF are crucially involved in activation of monocytic function, the data presented suggest that down-regulation of IFN-gamma-R by GM-CSF may represent a potential negative feedback control of monocyte activation. Further studies of IFN-gamma binding characteristics and isolation of IFN-gamma-R by immunoprecipitation revealed that IFN-gamma binding to human peripheral blood monocytes is mediated by a receptor protein structurally and functionally identical to that previously characterized in several established cell lines of other tissue origin.
Fischer
T
T
Klinische Arbeitsgruppe der Max-Planck-Gesellschaft, University of Göttingen, F.R.G.
Wiegmann
K
K
Böttinger
H
H
Morens
K
K
Burmester
G
G
Pfizenmaier
K
K
D015152:Blotting, Northern; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism*; D011233:Precipitin Tests; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D017471:Receptors, Interferon; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor