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IFN-gamma/lipopolysaccharide activation of macrophagesis associated with protein kinase c-dependent down-modulation of the colony-stimulating factor-1 receptor

: Stanley, E.R.; Baccarini, M.; Bartocci, A.; Büscher, D.; Dello Sbarba, P.

The Journal of immunology 149 (1992), No.9, pp.2656-2661
ISSN: 0022-1767
ISSN: 1048-3233
ISSN: 1047-7381
ISSN: 1550-6606
Journal Article
Fraunhofer ITA ( ITEM) ()
biological chemistry; cell culture; endotoxin; immunology; interferon; interferon gamma; macrophage; molecular biology; mouse; protein kinase

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.