Format

Send to

Choose Destination
J Immunol. 1996 Apr 1;156(7):2553-7.

Endogenous IFN-alpha beta suppresses colony-stimulating factor (CSF)-1-stimulated macrophage DNA synthesis and mediates inhibitory effects of lipopolysaccharide and TNF-alpha.

Author information

1
Department of Medicine, University of Melbourne, The Royal Melbourne Hospital, Victoria, Australia.

Abstract

Murine bone marrow-derived macrophages (BMM) are widely used as a suitable model to study the proliferative response to macrophage-CSF or CSF-1. We report here that the amount of DNA synthesis observed in BMM cultures in response to CSF-1 can be masked quite significantly by low levels of IFN-alpha beta produced in the cultures. It was found that Ab to IFN-alpha beta could enhance the proliferative response in CSF-treated BMM that were able to respond to endogenous IFN-alpha beta; however, BMM from mice lacking a component of the type I IFN receptor did not show any enhancement of CSF-1-dependent DNA synthesis on addition of the Ab. While DNA synthesis in CSF-1-stimulated BMM from normal mice was also very sensitive to the inhibitory actions of very low concentrations of added IFN-alpha beta, DNA synthesis in BMM from the "knockout" mice was not, indicating that the type I IFN receptor component containing the null mutation was essential for signal transduction. Previously it was shown that bacterial LPS, TNF-alpha, IFN-gamma, and cAMP could all inhibit CSF-1-stimulated BMM DNA synthesis and proliferation. Using the combined approach of blocking IFN-alpha beta Ab and the IFN receptor "knockout" mice, it was found here that the growth-inhibitory effects of LPS and TNF-alpha are due, to a significant extent, to endogenous IFN-alpha beta, whereas those of IFN-gamma and cAMP occur by a different mechanism. it is proposed that the type I IFN receptor (IFNAR 1) "knockout" mice may be useful in delineating some of the in vivo actions of CSF-1, LPS, TNF-alpha, and possibly other agents.

PMID:
8786318
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center