RII-dependent cytolysis
* Department of Internal Medicine, University of Genova Medical School, Genova, Italy; and
Department of Pathology, University of Southern California, Los Angeles, California
Correspondence: Prof. Franco Dallegri, Dipartimento di Medicina Interna e Specialità Mediche, Viale Benedetto XV n.6, I-16132 Genova, Italy. E-mail: MACROBUTTON HtmlResAnchor otto{at}csita.unige.it
Human neutrophils incubated with the anti-HLA-DR mAb Lym-1, plus PMA,
induced significant 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 stimulate neutrophil-respiratory burst. In fact, first,
neutrophils from a patient with chronic granulomatous disease were
cytolytically effective in spite of their inability to produce
oxidants. Second, various kinase inhibitors exerted different effects
on the PMA-stimulated cytolytic system and neutrophil-oxidative burst.
Previous studies have shown the involvement of the Fc
RII, CD11b-CD18
integrins, 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-FcRII 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 insensitive and sensitive to
inhibition by pertussis toxin, respectively. Thus, the use of PMA and
GM-CSF as neutrophil stimulants uncovers the existence of distinct
mechanisms of Lym-1 mAb-mediated cytolysis.
Key Words: human neutrophils • ADCC • Lym-1 • Fc receptors • GM-CSF • phorbol myristate acetate
