Induction of IFN-γ in macrophages by lipopolysaccharide

Abstract

In this paper we report that macrophages can be stimulated to express detectable levels of IFN-gamma-specific mRNA. Macrophages from lipopolysaccharide (LPS)-responsive, C3H/OuJ mice are induced by LPS to increase steady-state levels of IFN-gamma-specific mRNA, while those from LPS-hyporesponsive C3H/HeJ mice are not. This interstrain variation is apparently the result of LPS-specific signal differences since macrophages derived from both Lpsn and Lpsd mouse strains are able to produce comparable levels of IFN-gamma-specific mRNA following stimulation with polyinosinic-polycytidylic acid. The identity of the cell type responsible for this IFN-gamma message appears to be the macrophage as IFN-gamma-specific mRNA was also detectable following T and natural killer cell depletion, in the LPS-stimulated RAW 264.7 cell line, and in a homogeneous population of mature macrophages propagated in vitro by stimulation of bone marrow progenitors with recombinant colony stimulating factor-1. Immunofluorescent staining of fixed and permeabilized LPS-stimulated macrophages confirmed the presence of immunoreactive IFN-gamma protein. The possible significance of IFN-gamma production by macrophages is discussed in the context of normal macrophage differentiation as well as the inflammatory immune response.

Deletion of PPARγ in Alveolar Macrophages Is Associated with a Th-1 Pulmonary Inflammatory Response

“…Immunostaining demonstrated enhanced iNOS protein only in alveolar macrophages whereas IFN-␥ protein was present in both lymphocytes and macrophages. Expression of IFN-␥ has been noted previously in murine (25,26) and human (27) macrophages (reviewed in Ref. 28).…”

Cytokine regulation of expression of class I MHC antigens

“…In the human system, T cells that express the activation-dependent CD30 membrane antigen are the principal subset producing IFN-γ (Alzona et al, 1994). Recently production of IFN-γ by mononuclear phagocytes has also been described (Fultz et al, 1995).…”

In vivo role of IFN‐γ produced by antigen‐presenting cells in early host defense against intracellular pathogens

“…IFN-+ gene knockout (IFN-+ -/-) mice, IFN-+ receptor gene knockout (IFN-+ R -/-) mice, as well as other IFN-+ -related gene knockout mice are extremely susceptible to intracellular pathogens compared to SCID or wild-type (WT) mice [5][6][7][8][9][10][11][12][13]. Whereas NK cells among lymphoid cells had been believed to be a major source of IFN-+ during early phase of infection, we and others have shown that antigen-presenting cells (APC) such as dendritic cells (DC) and macrophages produce large amounts of IFN-+ in response to interleukin (IL)-12 that is produced by APC upon microbial infection [14][15][16][17][18][19][20][21][22][23][24][25][26][27]. In fact, amounts of IFN-+ produced by DC and macrophages are substantially larger than those produced by NK cells [14][15][16].…”