The Journal of Immunology, Vol 145, Issue 9 2914-2919, Copyright © 1990 by American Association of Immunologists

ARTICLES

Regulation of IFN-gamma-receptor expression in human monocytes by granulocyte-macrophage colony-stimulating factor

T Fischer, K Wiegmann, H Bottinger, K Morens, G Burmester and K Pfizenmaier
Klinische Arbeitsgruppe der Max-Planck-Gesellschaft, University of Gottingen, F.R.G.

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.