Neutrophil-mediated cytotoxicity triggered by immune complexes: the role of reactive oxygen metabolites.
Normal human neutrophils triggered by precipitating immune complexes (IC), soluble IC (sIC) or heat-aggregated IgG (HAIgG) displayed low levels of cytotoxicity towards nonsensitized target cells. Catalase, but not heated catalase, completely impaired this nonspecific cytotoxicity (NSC), suggesting a key role for hydrogen peroxide (H2O2) in the lysis of target cells. Superoxide dismutase (SOD) and certain HO. and 1O2 scavengers were unable to exert significant effects. Three haem-enzyme inhibitors, sodium azide, sodium cyanide and 3-amino-1,2,4-triazole did not decrease neutrophil NSC, but markedly enhanced it. This data suggest that the mechanism involved was not dependent upon myeloperoxidase (MPO). The analysis of neutrophil-mediated ADCC indicates that oxygen-dependent but MPO-independent mechanisms appeared to be operative in this system. It was also found that the microfilament disrupting agents, cytochalasin B (CB) and dihydrocytochalasin B (dhCB), as well as the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), significantly enhanced NSC. In contrast, these compounds partially inhibited ADCC. This cytotoxic system provides a suitable model to study events that may occur during the course of immune complex diseases and also permits the evaluation of alternative lytic mechanisms triggered through neutrophil Fc gamma receptors.
Geffner
J R
JR
Sección Inmunología, IIHEMA, Buenos Aires, Argentina.
Giordano
M
M
Palermo
M S
MS
Prat
A
A
Serebrinsky
G P
GP
Isturiz
M A
MA
D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D000936:Antigen-Antibody Complex / Q000276:immunology*; D003078:Colchicine / Q000494:pharmacology; D003571:Cytochalasin B / Q000031:analogs & derivatives / Q000494:pharmacology; D003599:Cytoskeleton / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism
D000936:Antigen-Antibody Complex; C024794:dihydrocytochalasin B; D003571:Cytochalasin B; D006861:Hydrogen Peroxide; D009195:Peroxidase; D010100:Oxygen; D003078:Colchicine