Role of oxygen intermediates in cytotoxicity: studies in chronic granulomatous disease

The ability of human neutrophils to lyse various target cells was investigated using cells from normal individuals and from patients with chronic granulomatous disease (CGD) whose cells lack the ability to form reactive oxygen intermediates (ROI). Cytolysis was stimulated by phorbol myristate acetate (PMA), rabbit antiserum, and a heteroantibody that binds to both the FcRII receptor of neutrophils and to the target. The PMA-activated CGD neutrophils were deficient compared to controls in killing both tumor and chicken erythrocyte (CRBC) targets at all effector-target ratios in 18-h assays. When CRBC were sensitized with rabbit antiserum, the normal cells still killed slightly more. When killing of CRBC was mediated by the heteroantibody, however, cytotoxicity of CGD neutrophils exceeded that of normal cells. CGD mononuclear cells (MNC) killed tumor cell targets as well as or better than normal MNC. Thus, PMA-mediated cytolysis appears to depend primarily upon the ability of the cell to generate ROI whereas antibody-mediated cytotoxicity and MNC-mediated lysis of tumor cells do not require ROI formation.