Endogeneous interferon alpha/beta produced by murine Kupffer cells augments liver-associated natural killing activity.
Nonparenchymal liver cells from untreated C3HeB/FeJ mice, when incubated in medium containing-10% fetal bovine serum or portal serum, produced significant amounts of interferon alpha/beta (IFN alpha/beta). In contrast, other cell populations (spleen, mononuclear blood cells and peritoneal cells) from C3HeB/FeJ mice or nonparenchymal liver cells from other strains of mice (C3H/HeJ, germ-free C3H/HeN and C57Bl/6J) produced little or no detectable IFN in fetal bovine serum under the same culture conditions. The cells in the nonparenchymal liver cell population responsible for IFN alpha/beta production were adherent, phagocytic, silica-sensitive, carbonyl-iron-sensitive, and Thy1.2-, presumably Kupffer cells or resident liver macrophages. IFN alpha/beta production by cultured Kupffer cells was not observed if medium containing fetal bovine serum or portal serum was treated with polymyxin B or if Kupffer cells were cultured in serum-free medium. This suggested that small amounts of endotoxin in fetal bovine or portal serum stimulated Kupffer cells to produce IFN alpha/beta. Possibly, Kupffer cells are in a different state of activation/maturation than peritoneal and splenic macrophages since the sensitivity of resident Kupffer cells from C3HeB/FeJ mice to the stimulatory effects of endotoxin. The endogenous production of IFN alpha/beta by Kupffer cells from C3HeB/FeJ mice can augment liver-associated natural killer (NK) activity against YAC-1 cells (4h) and induce liver-associated cytotoxic activity, not restricted by the major histocompatibility complex, against NK resistant P815 mastocytoma cells (18 h).
Werner-Wasik
M
M
Department of Medicine, State University of New York, Buffalo.
von Muenchhausen
W
W
Nolan
J P
JP
Cohen
S A
SA
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D002469:Cell Separation; D002474:Cell-Free System; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D007106:Immune Sera / Q000494:pharmacology; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007728:Kupffer Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D000276:Adjuvants, Immunologic; D007106:Immune Sera; D007370:Interferon Type I