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.