Two novel colony-stimulating factor 1 (CSF-1) properties: it post-transcriptionally inhibits interferon-specific induction of class II antigens and reduces the risk of fetal abortion.
Local production of 250 U/ml of Colony Stimulating Factor 1 (CSF-1) by decidual cells on the 11th day of murine pregnancy prompted us to investigate the role of this mononuclear phagocyte factor during gestation. We show that the presence of CSF-1 accounts for down-regulating induction of class II antigens on the placenta, antigens whose presence leads to fetal death. It is known from previous studies that gamma interferon (IFN-gamma) induces the expression of MHC-Ia antigens on the placenta causing thus fetal rejection due to an immune reaction the mother develops against the fetus. This Ia induction occurs both in vitro and in vivo, however, an extra dose of CSF-1, in addition to the physiological levels already present, overwhelms the ability of IFN-gamma to such induction and the embryos are rescued. Thus, CSF-1 appears to be an inhibitor of IFN-gamma induced class II expression, a property that may permit CSF-1 to be employed during gestation to safeguard the outcome of pregnancy and alleviate, by extrapolation to the human system, the recurrent abortion issue. This action, however, is not unique during gestation only. Other inducible IFN-gamma cells (WEHI-3, HL-60 and HeLa) are also blocked by CSF-1 not to express surface class II antigens, as it has been recently reported on glia cells. At the mRNA level, however, CSF-1 is unable to block class II induction, a finding that suggests a post-transcriptional regulation pattern.
Vassiliadis
S
S
Institute of Molecular Biology and Biotechnology (IMBB), Crete, Greece.
Athanassakis
I
I
D000022:Abortion, Spontaneous / Q000453:epidemiology; D000818:Animals; D002478:Cells, Cultured; D003656:Decidua / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011247:Pregnancy; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins; D012307:Risk Factors; D014407:Tumor Cells, Cultured
D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma