Macrophages as a source of tumoricidal activity (tumor-necrotizing factor)

Abstract

Macrophage-enriched peritoneal exudate cells from mice infected with Mycobacterium bovis BCG, macrophage-like tumor cells (PU 5-1.8) and peritoneal macrophages propagated in vitro with macrophage growth factor released tumoricidal activity into the culture medium within 2-3 h after stimulation with ng quantities of bacterial [Escherichia coli] lipopolysaccharide. The cytotoxic activities from each of the macrophage culture supernatants eluted from DEAE-Sephacel columns at a NaCl concentration of 200 mM exhibited a MW of 50,000-60,000 as estimated by gel filtration, were stable at 56.degree. C for 30 min and were active at a pH range of 6-10. A rabbit antiserum directed against serum-derived cytotoxic activity (tumor-necrotizing factor) from BCG-infected and lipopolysaccharide-challenged mice inhibited all of the cytotoxic activities generated in vitro. The macrophage-derived cytotoxins are identical with serum-derived cytotoxic factor, which further implies that the macrophage is the cellular source of tumor-necrotizing factor.