Different activation pathways involved in antibody-dependent and immune-complexes-triggered cytotoxicity mediated by neutrophils

GEFFNER JR; GIORDANO M; SEREBRINSKY G; ISTURIZ, MA

clinical and experimental immunology

Wiley

Año: 1988 vol. 74 p. 471 - 476

We have shown previously that normal human neutrophils triggered by immune complexes displayedsignificant levels of cytotoxicity towards non-sensitized target cells (non-specific cytotoxicity-NSC)(Geffner, J.R. et al. 1987). Despite the fact that NSC and antibody-dependent cellular cytotoxicity(ADCC) are both mediated through neutrophil FcyR and require the activation of the respiratoryburst, the cytolytic mechanisms involved in each case appear to be different. In order to analyse thepathways of activation involved in the induction of NSC and ADCC, we studied here some of themetabolic requirements associated with each cytotoxic function. Our results suggest that ADCC isdependent on Na+/H+ antiporter activity, de novo protein synthesis, availability ofexternal Ca2+ andcalmodulin activity, activation of phospholipase C and activation of protein kinase C. On the otherhand, NSC appears to be dependent on availability of external Ca2+ and calmodulin activity andactivation of phospholipase A2. These results indicate that different pathways of activation areinvolved in the induction of neutrophil-mediated ADCC and NSC.