Autoregulation by interferons provides an endogenous 'priming' signal for LPS-responsive macrophages

Abstract

RT-PCR technology was used to evaluate endogenous levels of IFN-α, β, and γ mRNA in macrophages derived from LPS-responsive (C3H/OuJ) and LPS-hyporesponsive (C3H/HeJ) mice. IFN mRNA levels were found to be consistently higher in the LPS-responsive macrophages. That these IFNs may be part of an autocrine loop is supported by the observations that treatment of macrophages, in vitro, with IFN-α or IFN-β induces IFN-γ mRNA and, conversely, that exogenous IFN-γ treatment results in increased detection of both IFN-a and IFN-β mRNA species. In vitro 'priming' of LPS-hyporesponsive macrophages with either IFN-α or IFN-γ causes these cells to be activated by a polyI:C triggering signal, in a manner equivalent to that seen for LPS-'primed' C3H/OuJ macrophages. Thus, low levels of endogenous IFNs, which induce each other bidirectionally, may provide a replenishable source of 'primed' macrophages, that are more plentiful in Lpsn mice and that are capable of being 'triggered' to functional maturity during an immune response.