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.