Human monocytes in a long-term culture with interleukin-2 show high tumoricidal activity against various tumor cells.
We compared the tumoricidal activity of human monocytes cultured with interleukin-2 (IL-2) or human recombinant interferon-gamma (IFN-gamma) alone, or IFN-gamma in combination with a small amount of lipopolysaccharides (LPS). Human monocytes cultured with IL-2 for 7 days or longer, termed lymphokine-activated macrophages (LAMs), showed higher tumoricidal activity than those cultured for 1 day. In contrast, monocytes cultured with IFN-gamma alone or in combination with LPS for 7 days or longer showed lower tumoricidal activity. LAMs were identified as macrophages by nonspecific esterase staining and immunofluorescence staining with anti-CD14 antibody. LAMs were not induced in fetal calf serum-containing medium, but they were induced when colony-stimulating factor-1 was added to the medium. LAMs showed high tumoricidal activity against all human and murine tumor cell lines tested, although they showed no cytotoxic activity against human normal cells. During incubation with IL-2, tumoricidal activity of LAMs was maximal at days 8-16 and was sustained until day 28. The difference in tumoricidal mechanism between LAMs and lymphokine-activated killer (LAK) cells was also shown by using two kinds of cytotoxic assay systems. LAMs require a long incubation time to kill tumor cells, but LAK cells can kill them immediately. Furthermore, LAMs kill tumor cells with complete DNA degradation, whereas LAK cells can induce significant but not complete DNA degradation. These results indicate that LAMs and LAK cells have different tumoricidal mechanisms for killing target cells, although they were induced by incubation with the same lymphokine, IL-2.
Higashi
N
N
Division of Chemical Toxicology and Immunochemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Nishimura
Y
Y
Higuchi
M
M
Osawa
T
T
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000378:metabolism; D004950:Esterases / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D007376:Interleukin-2; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D004247:DNA; D004950:Esterases