Changes in mechanisms of monocyte/macrophage-mediated cytotoxicity during culture. Reactive oxygen intermediates are involved in monocyte-mediated cytotoxicity, whereas reactive nitrogen intermediates are employed by macrophages in tumor cell killing.

Abstract

Freshly isolated human blood monocytes were spontaneously cytotoxic toward K562 tumor cells. During culture of the monocytes in vitro cytotoxicity decreased during the first 48 h but tumoricidal competence was restored after 3 to 4 days in vitro. These changes were accompanied by changes in both reactive oxygen intermediate generating capacity and reactive nitrogen intermediate production. Lucigenin-dependent chemiluminescence stimulated with either FMLP or PMA declined during the first 2 days in culture and was negligible during the later days in culture. Superoxide radical production in response to either FMLP or PMA remained fairly constant for the first few days in vitro and then declined. NO2- concentration in monocyte-conditioned medium was fairly constant during the first few days in vitro but increased after 6 days. The return to tumoricidal competence after 3 to 4 days in culture was decreased by the addition of NG-monomethyl-L-arginine. These results indicate that reactive oxygen intermediates are employed by monocytes in the killing of tumor cells. However, after maturation of monocytes to macrophages, this mechanism becomes less important and reactive nitrogen intermediates are employed in mediating macrophage cytotoxicity.