THE CYTOTOXIC CHARACTERISTICS OF TUMOR INFILTRATING MACROPHAGES AND PERIPHERAL BLOOD MONONUCLEAR CELLS

Macrophages, which play an important role in a host's defense against microorganisms, also demonstrate antitumor cytotoxicity after activation by various agents. In this study, we analyzed the cytokine requirements for activation of human blood monocytes for development of killing activity against tumor target cells. Peripheral human blood monocytes were cocultured with LPS, IFNg, ILg and IL15 for intervals up to 120 h. Lytic activity against melanoma cell lines was assessed in 18-h using 51Cr-release assay. Human peripheral blood monocytes after coculture with LPS, IFNg or the combination of both exhibited no lytic activity at any time points. However, after activation with IL2 and IL15 high, reproducible lytic activity occured. Addition of L-NMA, a competitive inhibitor of NOS, did not inhibit the generation of cytolytic activity. In simultaneous control studies, the same levels of L-NMA completely and reproducibly inhibited nitrite production, in response to IFNg.