MECHANISMS OF TUMOR-CELL DESTRUCTION BY PMA-ACTIVATED HUMAN-NEUTROPHILS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 48  (2) , 273-279
Abstract
Phorbol myristate acetate (PMA)-activated neutrophils destroyed B lymphoblast [human Burkitt''s lymphoma] tumor cells (Raji) as determined by the 51Cr release assay. The target cell lysis was prevented by azide, suggesting the involvement of the myeloperoxidase enzyme. Catalase and cytochrome c caused a marked impairment of the neutrophil-mediated cytolysis; superoxide dismutase significantly enhanced the target cell destruction. Hydrogen peroxide plays a key role in the target cell injury; superoxide anion appears to be devoid of direct cytotoxic activity, despite its requirement as a precursor of hydrogen peroxide. The target cell destruction required the presence of the iodide ion as oxidizable cofactor for the myeloperoxidase-hydrogen peroxide system. The chloride ion alone was uneffective. Inhibition of target cell metabolic pathways, involved in the cellular defenses against oxidative injury, by the antineoplastic agent 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) resulted in an increased neutrophil-mediated cytolysis. Under the experimental conditions used, PMA-activated neutrophils incubated with BCNU-treated Raji cells became cytotoxic also in the presence of the chloride ion alone as myeloperoxidase cofactor. Raji target cell destruction by PMA-activated neutrophils probably depends on the myeloperoxidase-hydrogen peroxide-halide system. The cytolytic events is influenced by target cells themselves, which should be regarded as an active component of the cytotoxic system, capable of interfering with the lytic mediators of the effector cells.