Interferon-gamma-dependent expression of inducible nitric oxide synthase, interleukin-12, and interferon-gamma-inducing factor in macrophages elicited by allografted tumor cells.
We have examined the mechanisms of activation of macrophages (Møs) induced by i.p. allografted Meth A tumor cells (Meth A-Møs) during the rejection of the cells by C57BL/6 mice. Inducible nitric oxide (NO) synthase (iNOS), interleukin-12 (IL-12), and interferon-gamma (IFN-gamma)-inducing factor (IGIF) were transiently expressed in Meth A-Møs during the rejection. The expression was impaired in mice in which the gene encoding IFN-gamma had been disrupted (IFN-gamma-/-). In vitro studies showed that Meth A-Møs from IFN-gamma +/+ mice induced an apoptotic type of cell death in P815 cells, without cell-to-cell contact, in an NO-dependent manner, whereas Meth A-Møs from IFN-gamma-/- mice could not lyse these cells. The iNOS, IL-12, and IGIF expression was also impaired in bacteria-activated Møs from IFN-gamma-/-mice, indicating that IFN-gamma, but not IGIF, would be the initial signal that leads to the activation of Møs in vivo.
Sanchez-Bueno
A
A
Department of Cell Biology, Osaka Bioscience Institute, Japan.
Verkhusha
V
V
Tanaka
Y
Y
Takikawa
O
O
Yoshida
R
R
D000818:Animals; D017209:Apoptosis; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004247:DNA / Q000032:analysis; D017931:DNA Primers; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005354:Fibrosarcoma / Q000201:enzymology / Q000276:immunology*; D015870:Gene Expression; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology*; D018664:Interleukin-12 / Q000096:biosynthesis*; D020382:Interleukin-18; D008264:Macrophages / Q000201:enzymology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009163:Mycobacterium bovis / Q000276:immunology; D009368:Neoplasm Transplantation; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D013997:Time Factors; D014184:Transplantation, Homologous; D019323:omega-N-Methylarginine
D016207:Cytokines; D017931:DNA Primers; D004791:Enzyme Inhibitors; D020382:Interleukin-18; D018664:Interleukin-12; D019323:omega-N-Methylarginine; D007371:Interferon-gamma; D004247:DNA; D001120:Arginine; D019001:Nitric Oxide Synthase