Neutrophil-mediated cytotoxicity triggered by immune complexes: the role of reactive oxygen metabolites

GEFFNER J; GIORDANO M; PALERMO M; PRAT A; SEREBRINSKY G; ISTURIZ, MA

clinical and experimental immunology

Wiley

Año: 1987

1365-2249

Normal human neutrophils triggered by precipitating immune complexes (IC), soluble IC(sIC) or heat-aggregated IgG (HAIgG) displayed low levels of cytotoxicity towardsnonsensitized target cells. Catalase, but not heated catalase, completely impaired thisnonspecific cytotoxicity (NSC), suggesting a key role for hydrogen peroxide (H202) in thelysis of target cells. Superoxide dismutase (SOD) and certain HO and 102 scavengers wereunable to exert significant effects. Three haem-enzyme inhibitors, sodium azide, sodiumcyanide and 3-amino-1,2,4-triazole did not decrease neutrophil NSC, but markedlyenhanced it. This data suggest that the mechanism involved was not dependent uponmyeloperoxidase (MPO). The analysis of neutrophil-mediated ADCC indicates thatoxygen-dependent but MPO-independent mechanisms appeared to be operative in thissystem. It was also found that the microfilament disrupting agents, cytochalasin B (CB)and dihydrocytochalasin B (dhCB), as well as the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (FM LP), significantly enhanced NSC. In contrast, thesecompounds partially inhibited ADCC. This cytotoxic system provides a suitable model tostudy events that may occur during the course of immune complex diseases and alsopermits the evaluation of alternative lytic mechanisms triggered through neutrophil Fcyreceptors