Monoclonal Lym-1 antibody-targeted lysis of B lymphoma cells by neutrophils. Evidence for two mechanisms of Fc gamma RII-dependent cytolysis

Human neutrophils incubated with the anti-HLA-DR mAb Lym-1, plus PMA, induc ed significant cytolysis of B lymphoma cells compared with Lym-1 and PMA al one. The effect of PMA was independent of the ability of the compound to st imulate neutrophil-respiratory burst. In fact, first, neutrophils from a pa tient with chronic granulomatous disease were cytolytically effective in sp ite of their inability to produce oxidants. Second, various kinase inhibito rs exerted different effects on the PMA-stimulated cytolytic system and neu trophil-oxidative burst. Previous studies have shown the involvement of the Fc gamma RII, CD11b-CD18 integrins, and CD66b glycoproteins in the Lym-1 m Ab-dependent cytolysis by GM-CSF-stimulated neutrophils. The present PMA-st imulated system was inhibited by the anti-Fc gamma RII mAb IV.3, the anti-C D18 mAb MEM 48, and the anti-CD11b mAb 2LPM19c but not by the anti-CD66b mA b 80H3 and N-acetyl-D-glucosamine. Furthermore, the PMA- and GM-CSF-stimula ted cytolysis was insensitive and sensitive to inhibition by pertussis toxi n, respectively. Thus, the use of PMA and GM-CSF as neutrophil stimulants u ncovers the existence of distinct mechanisms of Lym-1 mAb-mediated cytolysi s.