IFN-gamma/lipopolysaccharide activation of macrophages is associated with protein kinase C-dependent down-modulation of the colony-stimulating factor-1 receptor.
IFN gamma/LPS treatment increases macrophage tumoricidal and microbicidal activity and inhibits CSF-1-induced macrophage proliferation. The mechanism underlying the latter effect was investigated in the CSF-1-dependent mouse macrophage cell line, BAC-1.2F5. IFN-gamma and LPS together dramatically reduced the total number of CSF-1 receptors (CSF-1R) via selective degradation of the cell surface form. Processing and transport of intracellular CSF-1R to the cell surface were unaffected. IFN-gamma alone had no effect but significantly enhanced LPS-induced CSF-1R down-regulation. The reduction in CSF-1R number was protein kinase C-dependent and involved changes in serine phosphorylation of the receptor at different sites. CSF-1R down-modulation by this mechanism may be important in switching off the energy-consuming processes of CSF-1R-mediated proliferation and chemotaxis in activated macrophages.
Baccarini
M
M
Department of Developmental Biology and Cancer, Albert Einstein College of Medicine New York, NY 10461.
Dello Sbarba
P
P
Buscher
D
D
Bartocci
A
A
Stanley
E R
ER
D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000187:drug effects*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000032:analysis* / Q000378:metabolism
D008070:Lipopolysaccharides; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016186:Receptor, Macrophage Colony-Stimulating Factor; D011493:Protein Kinase C