EFFECTS OF THE MURINE L929 AND L1210 CELL-LINES ON NITRIC-OXIDE AND TNF-ALPHA PRODUCTION BY RAW-264.7 MURINE MACROPHAGES

Co-cultures of the murine macrophagic cell line RAW 264.7 with the L92 9 fibrosarcoma cell line, but not with the leukemia L1210 cell line, s howed enhanced NO production over control RAW 264.7 cells. This potent iating effect, which was observed in detectably mycoplasma-free condit ions and required low concentrations of recombinant murine IFN-gamma, was due to soluble factors released from L929 cells and not to physica l contact between the two cell types. The soluble factors were able to induce TNF-alpha in the macrophages and to potentiate the TNF-alpha r elease induced by IFN-gamma. increased generation of NO in RAW 264.7 c ells co-cultured with L929 cells was prevented by a neutralizing anti- TNF-alpha antibody, suggesting that TNF-alpha is an autocrine factor f or iNOS expression in these conditions. Also the L929 cell line showed a 4- to B-fold enhanced NO production following co-culture with RAW 2 64.7 cells, thus indicating that exposure of tumor cells to macrophage s can lead to an increased NOS expression in tumor cells themselves. ( C) 1997 Academic Press