IFN-gamma/lipopolysaccharide activation of macrophagesis 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 reductionin 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 ins switching off the energy-consuming processes of CSF-1R-mediated proliferation and chemotaxis in activated macrophages.