Human pulmonary macrophage tumor cell cytotoxicity.

In vivo animal studies support the concept that monocytes and macrophages are important in the immune surveillance of oncogenesis and in vitro activated murine macrophages are cytocidal for tumor cells. In this study. we examined human pulmonary macrophage and blood monocyte tumor cell cytotoxicity (a measure of cytostasis and cell kill) and cytocidal activity (cell kill). Three human tumor cell lines and a skin fibroblast cell strain were used. Pulmonary macrophages exhibited significantly more cytocidal and cytotoxic activity than blood monocytes against all three tumor cell lines tested. In addition, blood monocytes from patients with pulmonary infection and neoplasm were significantly more cytotoxic than monocytes from normal individuals (p < 0.01 ). A similar trend was observed when pulmonary macrophages were studied, but the differences were not statistically significant (p = 0.1 ). Pulmonary macrophages also exhibited limited cytocidal activity against human fibroblasts. However, cytocidal activity against fibroblasts but not tumor cells was abrogated by decreasing macrophage concentration in the assay system. Macrophage cytocidal activity against fibroblasts but not tumor cells could be inhibited by catalase and enhanced by phorbol myristate acetate. These data suggest that (A) in vivo maturation of monocytes to macrophages is associated with enhanced tumorcidal activity. (B) alteration of the in vivo microenvironment by tumors or infection enhances blood monocyte and perhaps pulmonary macrophage tumor cell cytotoxicity. (C) human pulmonary macrophages exhibit specific cytocidal activity against tumor cells in vitro, which is not due to production of H202.