Interferon-induced inhibition of receptor-mediated endocytosis of colony-stimulating factor (CSF-1) by murine peritoneal exudate macrophages.
Apart from its characteristic antiviral activity, interferon (IFN) also exerts a variety of biologic effects on macrophages. We have studied the effect of IFN on the expression of the colony-stimulating factor receptors (CSF-1 receptors) by murine peritoneal exudate macrophages (PEM). At 37 degrees C, murine IFN decreased the expression of the CSF-1 receptor activity in a time- and dose-dependent fashion by PEM from both endotoxin-sensitive (C3H/Sn) and endotoxin-resistant strains (C3H/HeJ) of mice. Scatchard analysis from the binding data suggests that the decreased expression of CSF-1 receptors is a result of decreased number of receptors rather than a decreased binding affinity. When IFN was incubated with anti-IFN before the addition to cultures, the effect was completely abolished indicating that this activity resides in the same molecules as IFN. The suppressed CSF-1 receptor activity on PEM by IFN appeared to be stable. Removal of added IFN never resulted in a full recovery of CSF-1 binding activity by PEM even after prolonged incubation (7 days). IFN also inhibited the receptor-mediated uptake and utilization of CSF-1 molecules by treated cells, which appeared to be a direct effect of the decreased number of CSF-1 receptors. Treatment of PEM with dexamethasone, prostaglandin, transferrin, insulin, or dibutyryl cAMP failed to suppress both the expression of CSF-1 receptors and CSF-1 utilization by PEM. These studies suggest that IFN may play a role in the regulation of both macrophage production and differentiation via the modulation of specific membrane receptors and inhibition of receptor-mediated CSF-1 endocytosis.
D000818:Animals; D001667:Binding, Competitive; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects*; D005260:Female; D007370:Interferon Type I / Q000494:pharmacology*; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010529:Peritoneal Cavity / Q000166:cytology; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D016184:Receptors, Colony-Stimulating Factor
D003115:Colony-Stimulating Factors; D007370:Interferon Type I; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor