PT  - JOURNAL ARTICLE
AU  - Bonvini, E
AU  - Hoffman, T
AU  - Herberman, R B
AU  - Varesio, L
TI  - Selective augmentation by recombinant interferon-gamma of the intracellular content of S-adenosylmethionine in murine macrophages.
DP  - 1986 Apr 01
TA  - The Journal of Immunology
PG  - 2596--2604
VI  - 136
IP  - 7
4099  - http://www.jimmunol.org/content/136/7/2596.short
4100  - http://www.jimmunol.org/content/136/7/2596.full
SO  - J. Immunol.1986 Apr 01; 136
AB  - 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.