title: Tumor killing by human alveolar macrophages and blood monocytes. Decreased cytotoxicity of human alveolar macrophages.
abstract: Tumor killing by human alveolar macrophages (AM) might be an important mechanism of pulmonary defense against neoplastic disease. We compared AM and blood monocytes (Mo) for the ability to kill 2 neoplastic targets, A549 human lung adenocarcinoma cells and P815 mastocytoma cells. Blood monocytes were able to kill both targets, whereas AM killed neither. Tumor killing by Mo was spontaneous and was not increased by incubation with lipopolysaccharide. Because the P815 target is highly sensitive to lysis by hydrogen peroxide (H2O2), it afforded the opportunity to compare AM and Mo for the ability to kill tumors by the production of toxic oxygen compounds. Comparable amounts of superoxide anion were produced by AM and Mo after stimulation with phorbol myristate acetate. However, luminol-enhanced chemiluminescence of AM was far less than that of Mo, suggesting that AM could not utilize the myeloperoxidase-H2O2-halide ion system for tumor killing. The addition of exogenous peroxidase to cultures of AM and P815 cells enabled AM to kill this tumor cell. Our results suggest that as Mo mature into AM, their ability to kill tumor cells declines and that AM may be unable to kill H2O2-sensitive tumors because of a loss of myeloperoxidase during maturation.
mesh_terms: D000818:Animals; D000838:Anions; D001386:Azides / Q000494:pharmacology; D002283:Carcinoma, Bronchogenic / Q000276:immunology / Q000473:pathology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008163:Luminescent Measurements; D008165:Luminol / Q000494:pharmacology; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010544:Peroxidases / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology*; D012513:Sarcoma, Experimental / Q000276:immunology*; D019810:Sodium Azide; D013481:Superoxides / Q000096:biosynthesis
chemical_list: D000838:Anions; D001386:Azides; D007527:Isoenzymes; D008070:Lipopolysaccharides; D013481:Superoxides; D008165:Luminol; D019810:Sodium Azide; D010544:Peroxidases; D009195:Peroxidase