Selective augmentation by recombinant interferon-gamma of the intracellular content of S-adenosylmethionine in murine macrophages.
Treatment of mouse peritoneal macrophages with IFN-gamma augmented the intracellular content of S-adenosylmethionine, as measured by quantitative high-performance liquid chromatography. Accumulation of S-adenosylhomocysteine, a competitive product of S-adenosylmethionine, was not detectable, either by direct measurement of absorbance or by radioisotopic techniques in IFN-gamma-treated macrophages. However, accumulation of S-adenosylhomocysteine was observed after treatment of macrophages with known inhibitors of S-adenosylhomocysteine catabolism. No inhibition of phospholipid methylation was observed upon IFN-gamma treatment, indicating that no reduction of the S-adenosylmethionine to S-adenosylhomocysteine ratio is induced by IFN-gamma in murine macrophages. The increased content of S-adenosylmethionine was associated with the acquisition of tumoricidal activity by macrophages upon IFN-gamma treatment. LPS also augmented the cellular content of S-adenosylmethionine and activated macrophages to become cytotoxic, suggesting a common mechanism of action for IFN-gamma and LPS in macrophage activation. Treatment of macrophages with cycloleucine, an agent that induces depletion of cellular S-adenosylmethionine, made the macrophages refractory to induction of cytolytic activity by IFN-gamma, suggesting a critical role for S-adenosylmethionine in macrophage activation.
Bonvini
E
E
Hoffman
T
T
Herberman
R B
RB
Varesio
L
L
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity; D010743:Phospholipids / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*; D012436:S-Adenosylmethionine / Q000096:biosynthesis / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D010743:Phospholipids; D011994:Recombinant Proteins; D012436:S-Adenosylmethionine; D007371:Interferon-gamma