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Title: IFN-gamma reduces specific binding of tumor necrosis factor on murine macrophages

Journal Article · · Journal of Immunology; (USA)
OSTI ID:6057628
;  [1]
  1. U 196 INSERM, Institut Curie, Paris (France)

Because IFN-gamma is the main cytokine activating macrophages and TNF cooperates in this activation, we assessed TNF binding capacity during the course of murine macrophage activation by IFN-gamma. TNF binding to elicited macrophages increased with time, was maximal by 8 h of culture, and required de novo protein synthesis. {sup 125}I-TNF bound to about 40,000 sites/cell with a Kd of 1 x 10(-9) M. Cross-linking experiments performed with a bifunctional cross-linking agent revealed a specific band with a m.w. of 94,000. Preincubation of macrophages with IFN-gamma prevented the binding of TNF to receptors. This effect was dose-dependent and maximal at 100 U/ml. IFN-gamma also reduced specific TNF binding to preexisting receptors (50% inhibition in 3 h), but IFN-gamma did not change the internalization rate of TNF. These studies showed that the number of TNF receptors increased on macrophages vs maturation in culture and was negatively controlled by IFN-gamma.

OSTI ID:
6057628
Journal Information:
Journal of Immunology; (USA), Vol. 146:4; ISSN 0022-1767
Country of Publication:
United States
Language:
English