Cytotoxic activity of human monocytes towards sensitized red cells is not dependent on the generation of reactive oxygen species

The purpose of this investigation was to test whether the generation of oxygen radicals is required for the cytotoxic activity of human monocytes. The cytotoxic activity of human monocytes was measured as the capacity to lyse, in vitro, human red cells sensitized with non-complement-binding IgG anti-D alloanti-bodies. Lysis was determined by measuring 51Cr release from the red cells. Studies were performed with monocytes from patients with chronic granulomatous disease (CGD). In contrast with normal neutrophils, phagocytosing neutrophils from these patients are unable to generate oxygen radicals, hydrogen peroxide, or singlet oxygen. We found that monocytes from CGD patients were similarly incapable of generating these reactive oxygen species during phagocytosis. This indicates that, like neutrophils, monocytes from CGD patients are defective in the generation of activated oxygen products. Despite this defect, monocytes from CGD patients displayed a normal cytotoxic activity towards sensitized red cells. In addition, neither scavengers of superoxide, hydrogen peroxide, hydroxyl radicals, or singlet oxygen, nor inhibitors of myeloperoxidase, had any effect on the cytotoxic activity of normal monocytes. Together, these results indicate that the cytotoxic activity of human monocytes towards sensitized red cells is not dependent on the generation of reactive oxygen derivatives.