Abundant Production of Nitric Oxide from Murine Macrophages by Direct Stimulation of Tumor Cells

Abstract

By the coculture of tumor cells and resident murine peritoneal macrophages, we found that P1HTR tumor cells, which were the subline of P815 mastocytoma, stimulated syngeneic or allogeneic peritoneal macrophages to produce nitric oxide. This nitric oxide in turn kills P1HTR target cells. The cytotoxicity and nitric oxide production were completely abolished by the addition of L-arginine homologue NG-monometyl-L-arginine. The original P815 tumor cells had only weak activity to stimulate macrophages to produce nitric oxide and were weekly killed by coculture of P815 and resident macrophages. Macrophage cell line, RAW264-7, was also stimulated to produce nitric oxide by P1HTR cells. The ability to stimulate macrophages to produce nitric oxide resided on the membranous fragment of P1HTR cells.