Macrophage activation by interferon α + β is associated with a loss of proliferative capacity: Role of interferon α + β in the regulation of macrophage proliferation and function

Abstract

Murine peritoneal exudate macrophages (PEM) can be induced by colony-stimulating factor (CSF-1) to undergo extensive proliferation and colony formation in vitro. In the presence of Interferon α + β (IFN α + β) the proliferative capacity of PEM was greatly suppressed in a dose-dependent manner. The antiproliferative activity of IFN α + β appears to be noncytocidal and reversible at low concentrations. At higher concentrations, exposure to IFN α + β was sufficient to cause growth inhibition in PEM. Tissue-derived PEM were at least 25-fold more sensitive than bone marrow GM-CFC to the antiproliferative activity of IFN α + β. The fact that bone marrow-derived adherent cells also exhibited a higher degree of sensitivity than the less differentiated nonadherent counterparts suggests that the primary targets of IFN α + β are cells derived from a later stage of development. Concomitantly with the loss of proliferative activity, both the tumoricidal and Fc receptor-mediated phagocytic activities in IFN α + β treated PEM were greatly enhanced. These effects could be completely neutralized by the addition of anti-IFN α + β immunoglobulin, indicating that they are mediated by the same molecule. This remarkable dichotomy in the actions of IFN α + β (stimulates functional activities but suppresses proliferative capacity) suggests that IFN α + β may play a role in the regulation of macrophage production and function.