Autocrine Induction of Macrophage Synthesis of Complement Subcomponent Clq by Endogenous Interferon-α/β

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Abstract
Peritoneal macrophages (Mø) constitutively synthesize and secrete interferon-α (IFN-α) and IFN-β, as well as complement subcomponent Clq. Because exogenous interferon-γ (IFN-γ) stimulates Mø synthesis of Clq, our purpose was to determine if endogenous secretion of IFN-α/β regulated the constitutive level of endogenous Clq mRNA synthesis in an autocrine fashion. Both exogenous IFN-α and IFN-β effectively substituted for IFN-γ in stimulating Mø Clq mRNA expression in a dose-dependent fashion by northern blot analysis. Neutralizing anti-INF-α/β antibodies inhibited Mø constitutive Clq mRNA synthesis by approximately twofold and abrogated the feedback stimulatory effects of exogenous Clq on Clq mRNA expression. Paraffin oil-elicited inflammatory Mø displayed distinctively different constitutive levels of Clq mRNA expression from thioglycollate brothelicited Mø, which was correlated with their relative levels of secretory IFN-α/β by ELISA. Exogenous IFN-α/β also restored Clq mRNA synthesis of AKR mouse Mø with low constitutive Clq mRNA expression. The cumulative results support the concept that constitutive synthesis of Clq by Mø is regulated by the endogenous synthesis and secretion of IFN-α/β, which appears to act in an autocrine fashion.