Neutrophil-mediated antibody-dependent cellular cytotoxicity against erythrocytes. Mechanisms of target cell destruction.
Human neutrophils were cytotoxic to IgG coated ox erythrocytes as determined by a 51Cr release assay. Target cell phagocytosis was found to take place during the cytotoxic reaction, suggesting that cytolysis occurs as a post-phagocytic event. Studies, performed with neutrophils from patients with chronic granulomatous disease, demonstrated that these cells had an impaired cytotoxic activity, despite their ability to normally ingest target cells. Thus the cytotoxicity of human neutrophils against sensitized ox erythrocytes depends mainly on oxidative mechanisms. Oxygen radical scavengers failed to prevent the target cell lysis, possibly because of their inability to gain access into the killing sites. However, when cytotoxicity was carried out in presence of latex particles, pre-incubated with oxygen radical scavengers, a significant inhibition of target cell lysis by superoxide dismutase and cytochrome c was obtained. As well, in these experimental conditions, catalase had no effect. Furthermore, cytotoxicity was unaffected by hemeprotein inhibitors, cyanide and azide. Together, these results indicate that superoxide anion plays a key role in the neutrophil-mediated cytotoxicity against ox erythrocytes, whereas hydrogen peroxide alone or in combination with myeloperoxidase is unoperative under the experimental conditions employed.