INDUCTION OF IFN-GAMMA IN MACROPHAGES BY LIPOPOLYSACCHARIDE

In this paper we report that macrophages can be stimulated to express detectable levels of IFN-gamma-specific mRNA. Macrophages from lipopol ysaccharide (LPS)-responsive, C3H/OuJ mice are induced by LPS to incre ase steady-state levels of IFN-gamma-specific mRNA, while those from L PS-hyporesponsive C3H/HeJ mice are not. This interstrain variation is apparently the result of LPS-specific signal differences since macroph ages derived from both Lps(n) and Lps(d) mouse strains are able to pro duce comparable levels of IFN-gamma-specific mRNA following stimulatio n with polyinosinic - polycytidylic acid. The identity of the cell typ e responsible f or this IFN-gamma message appears to be the macrophage as IFN-gamma-specific mRNA was also detectable following T and natura l killer cell depletion, in the LPS-stimulated RAW 264.7 cell line, an d in a homogeneous population of mature macrophages propagated in vitr o by stimulation of bone marrow progenitors with recombinant colony st imulating factor-1. Immunofluorescent staining of fixed and permeabili zed LPS-stimulated macrophages confirmed the presence of immunoreactiv e IFN-gamma protein. The possible significance of IFN-gamma production by macrophages is discussed in the context of normal macrophage diffe rentiation as well as the inflammatory immune response.