Natural cytotoxicity on tumour cells of human macrophages obtained from diverse anatomical sites

Human mononuclear phagocytes were isolated from peripheral blood, peritoneal exudate and early lactation milk by adherence on microexudate-coated plastic and exposure to ethylene diamine tetracetic acid. Their cytolytic activity was measured as ³H-thymidine release from prelabelled target cells over 48-72 hr and cytostasis was evaluated in a spectrophotometric 72-hr assay. The murine SV40-transformed mKSA-TU5 line and the human E cell line, derived from an ovarian carcinoma, were employed as targets. Peripheral blood monocytes, in vitro-matured monocyte-derived macrophages, peritoneal macrophages and milk macrophages were all significantly cytolytic and cytostatic on these target cells at attacker to target cell ratios ranging from 5:1 to 40:1. When monocytes were cultivated in vitro, no loss of cytocidal capacity occurred over the first 10 days of culture, whereas later on, when epithelioid and giant cells predominate in the cultures, mononuclear phagocytes had little cytotoxic activity. Adherent cells obtained from cord blood or from the peripheral blood of old donors had natural cytotoxicity similar to monocytes obtained from young adult volunteers. Peripheral blood monocytes and peritoneal macrophages showed enhanced cytolytic activity after exposure to partially purified human fibroblast interferon. These experiments suggest that in the human mononuclear phagocyte series cytotoxicity on tumour cells is not restricted to circulating monocytes but is also expressed by macrophages obtained from diverse anatomical sites.