ANTIBODY-DEPENDENT AND ANTIBODY-INDEPENDENT CYTO-TOXICITY OF HUMAN MONONUCLEAR PHAGOCYTES - DEFECTIVE STIMULATION OF TUMORICIDAL ACTIVITY IN MILK MACROPHAGES

Abstract

Human peripheral blood monocytes, milk macrophages and peritoneal exudate macrophages were purified by adherence. Antibody-dependent cellular cytotoxicity (ADCC) was measured using the murine TLX9 lymphoma pre-labeled with 3H-thymidine. Direct, antibody-independent tumoricidal activity was measured against the murine TU5 line pre-labeled with 3H-tymidine. All mononuclear phagocyte populations tested were similary effective in mediating ADCC against TLX9 cells. In the absence of deliberate stimulation blood monocytes and peritoneal macrophages had appreciable spontaneous cytotoxicity against the susceptible TU5 line. Four of 10 milk macrophage preparations lacked detectable spontaneous killing activity on this target. In vitro exposure to partially purified fibroblast interferon (IFN) or to lymphokine supernatants from PHA[phytohemagglutinin] stimulated lymphocytes augmented the direct tumoricidal activity of blood monocytes and peritoneal exudate macrophages. Milk macrophages were completely unresponsive to IFN and lymphokines. The capacity to mediate antibody-dependent and -independent cytotoxicity against tumor cells can be dissociated to some extent in human mononuclear phagocyte populations from diverse anatomical sites.