Autocrine induction of macrophage synthesis of complement subcomponent C1q by endogenous interferon-alpha/beta.
Peritoneal macrophages (M phi) constitutively synthesize and secrete interferon-alpha (IFN-alpha) and IFN-beta, as well as complement subcomponent C1q. Because exogenous interferon-gamma (IFN-gamma) stimulates Mø synthesis of C1q, our purpose was to determine if endogenous secretion of IFN-alpha/beta regulated the constitutive level of endogenous C1q mRNA synthesis in an autocrine fashion. Both exogenous IFN-alpha and IFN-beta effectively substituted for IFN-gamma in stimulating M phi C1q mRNA expression in a dose-dependent fashion by northern blot analysis. Neutralizing anti-INF-alpha/beta antibodies inhibited M phi constitutive C1q mRNA synthesis by approximately twofold and abrogated the feedback stimulatory effects of exogenous C1q on C1q mRNA expression. Paraffin oil-elicited inflammatory M phi displayed distinctively different constitutive levels of C1q mRNA expression from thioglycollate brothelicited M phi, which was correlated with their relative levels of secretory IFN-alpha/beta by ELISA. Exogenous IFN-alpha/beta also restored C1q mRNA synthesis of AKR mouse M phi with low constitutive C1q mRNA expression. The cumulative results support the concept that constitutive synthesis of C1q by M phi is regulated by the endogenous synthesis and secretion of IFN-alpha/beta, which appears to act in an autocrine fashion.
Kolosov
M
M
Oklahoma Medical Research Foundation, Noble Center for Biomedical Research, Oklahoma City 73104-5046, USA.
Kolosova
I
I
Zhou
A
A
Leu
R W
RW
D000818:Animals; D000937:Antigen-Antibody Reactions; D001483:Base Sequence; D015922:Complement C1q / Q000096:biosynthesis* / Q000235:genetics; D005246:Feedback; D016898:Interferon-alpha / Q000378:metabolism / Q000502:physiology*; D016899:Interferon-beta / Q000378:metabolism / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation
D016898:Interferon-alpha; D012333:RNA, Messenger; D016899:Interferon-beta; D015922:Complement C1q