Mechanism of leukemic cell lysis by activated human macrophages: leukemic cells can be lysed without direct contact.

We recently reported that human macrophages effectively destroyed leukemic cells. In this study, we investigated the mechanism of leukemic cell lysis by human macrophages. Human peripheral blood monocyte-derived macrophages were activated with interferon-gamma and lipopolysaccharide. Activated macrophages exhibited lytic activity against leukemic cells (K562 and HL-60 cells) by cocultivation. When macrophages and these leukemic cells were separated by a microporous membrane, activated macrophages did not show any lytic activity against these leukemic cells. However, activated macrophages interacting with leukemic cells under the microporous membrane exhibited lytic activity against leukemic cells that were placed on the microporous membrane. Different kinds of leukemic cells were also effective to induce such lytic activity in the macrophages, but normal lymphocytes could not. Culture supernatants of activated macrophages incubated with leukemic cells did not have cytolytic activity against leukemic cells. The leukemic cells used in this study were confirmed to be resistant to tumor necrosis factor (TNF), but the activated macrophage-mediated cytolytic activity was significantly inhibited by the anti-TNF antibody. These findings suggested that the contact between macrophages and leukemic cells triggered the secretion of lytic factor(s), and that TNF and other labile factor(s) co-operatively functioned to lyse leukemic cells.