Free oxygen radicals are not detectable by chemiluminescence during human natural killer cell cytotoxicity

Mononuclear cells isolated from peripheral blood of normal donors produce free oxygen radicals (FR), detectable by chemiluminescence (CL), when interacting with target cells during natural killer (NK) cell lysis. FR-producing cells were found to have monocyte characteristics and gave a positive CL reaction when mixed at low concentration (0.5%) with purified NK cells. No correlation was found between susceptibility to NK cell lysis and capacity to induce CL with different target cell lines. Using high and low molecular FR scavengers, no NK cell inhibition was seen with superoxide dismutase, cytochrome c, and catalase, whereas some inhibition was seen with 4,5-dihydroxy-m- benzenedisulphonic acid (Tiron) and 2,3-dihydroxybenzoate. These compounds, however, required higher concentrations than used for inhibition of CL, suggesting an alternative action of these compounds. Normal levels of NK cell activity were found in two patients with chronic granulomatous disease, who were genetically incapable of producing detectable amounts of FR. As a result, it is concluded that human NK cells do not produce large amounts of FR during killing and that FR are unlikely to be the lytic end product. Nevertheless, neither a low degree of FR formation in NK cells nor a more subtle signal-transmitting role of FR during NK cell triggering can be excluded.