Toxic oxygen species in monocyte-mediated antibody-dependent cytotoxicity.

Abstract

The role of toxic oxygen species in monocyte-mediated ADCC against the myelogenous cell line K-562 was investigated. Freshly isolated human monocytes caused 40% specific lysis of antibody-coated K-562 cells (Ab-K-562). Monocytes challenged with Ab-K-562 gave a small but definite luminol-dependent chemiluminescence response, indicating that a respiratory burst with generation of toxic oxygen species had been elicited. Generation of hydrogen peroxide in areas of close apposition between the monocyte and the Ab-K-562 plasma membranes was demonstrated by electron microscopy using precipitation of cerium ions as a cytochemical stain for hydrogen peroxide. Catalase inhibited the formation of cerium precipitates in the interaction zone between monocytes and Ab-K-562 cells. Despite evidence that toxic oxygen species were generated, the monocytes' cytolytic activity against Ab-K-562 was not inhibited by superoxide dismutase, catalase, or azide. Enzymatically generated fluxes of superoxide anion or hydrogen peroxide were not cytolytic to K-562 cells but did have a cytostatic effect. We conclude that toxic oxygen species are generated when human monocytes are challenged with Ab-K-562. However, these toxic oxygen species do not appear to be the major mediators of the monocytes' cytolytic activity in this experimental system.