Stimulation of Macrophage Synthesis of Complement Clq by Interferon-γ Mediated by Endogenous Interferon-α/β

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Abstract
Both exogenous interferon-gamma (IFN-gamma) and interferon-alpha/beta (IFN-alpha/beta) stimulate C1q mRNA synthesis in murine macrophages. Previous studies suggested that IFN-gamma induced endogenous synthesis of IFN-alpha/beta by murine macrophages. In the present study, we determined the indirect effect of IFN-gamma on macrophage synthesis of C1q mRNA mediated by endogenous IFN-alpha/beta production. Upregulation of macrophage synthesis of C1q mRNA by both IFN-gamma and IFN-alpha/beta was reversed by neutralizing antibody to IFN-alpha/beta but not by nonimmune control serum. IFN-gamma was confirmed by ELISA to stimulate a six- to eightfold increase in macrophage secretion of IFN-alpha/beta compared with untreated control cells. We tentatively conclude that IFN-gamma stimulates macrophage synthesis and secretion of IFN-alpha/beta, which in turn promotes C1q mRNA synthesis in an autocrine or paracrine manner. Thus, exogenous IFN-gamma, derived from activated T lymphocytes, may act primarily on the macrophage to stimulate the endogenous synthesis of IFN-alpha/beta for autocrine modulation of a variety of biologic functions, including C1q synthesis.