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

Human neutrophils incubated with the anti-HLA-DR mAb Lym-1, plus PMA, induced sig- nificant cytolysis of B lymphoma cells compared with Lym-1 and PMA alone. The effect of PMA was independent of the ability of the compound to stim- ulate neutrophil-respiratory burst. In fact, first, neutrophils from a patient with chronic granuloma- tous disease were cytolytically effective in spite of their inability to produce oxidants. Second, vari- ous kinase inhibitors exerted different effects on the PMA-stimulated cytolytic system and neutro- phil-oxidative burst. Previous studies have shown the involvement of the FcgRII, CD11b-CD18 in- tegrins, and CD66b glycoproteins in the Lym-1 mAb-dependent cytolysis by GM-CSF-stimulated neutrophils. The present PMA-stimulated system was inhibited by the anti-FcgRII mAb IV.3, the anti-CD18 mAb MEM 48, and the anti-CD11b mAb 2LPM19c but not by the anti-CD66b mAb 80H3 and N-acetyl-D-glucosamine. Furthermore, the PMA- and GM-CSF-stimulated cytolysis was in- sensitive and sensitive to inhibition by pertussis toxin, respectively. Thus, the use of PMA and GM- CSF as neutrophil stimulants uncovers the exis- tence of distinct mechanisms of Lym-1 mAb-medi- ated cytolysis. J. Leukoc. Biol. 68: 662-668; 2000.