Toxic oxygen species in monocyte-mediated antibody-dependent cytotoxicity.
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.
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D001386:Azides / Q000494:pharmacology; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000096:biosynthesis; D007942:Leukemia, Experimental; D008163:Luminescent Measurements; D008854:Microscopy, Electron; D009000:Monocytes / Q000276:immunology*; D010100:Oxygen / Q000633:toxicity*; D010586:Phagocytes / Q000187:drug effects; D015054:Zymosan / Q000494:pharmacology
D001386:Azides; D003571:Cytochalasin B; D015054:Zymosan; D006861:Hydrogen Peroxide; D010100:Oxygen