CYTOPLASMIC CALCIUM FLUXES INDUCED IN CYTOTOXIC EFFECTOR-CELLS BY ENGAGEMENT OF FC-GAMMA RECEPTOR-I, RECEPTOR-II, AND RECEPTOR-III

Changes in the intracellular calcium ion concentration ([Ca2+]i) of monocytes, granulocytes, and NK cells have been studied following either (1) independent cross-linking of Fc-gamma receptors (Fc-gamma-R) I, II, or III, with F(ab-gamma')2 fragments of monoclonal antibodies; or (2) linking of a selected Fc-gamma-R to a tumour cell target with bispecific F(ab'gamma)2 antibodies. Upon cross-linking each Fc-gamma-R with antibody an increase in the [Ca2+]i was observed, although all receptors apart from Fc-gamma-RIII on NK cells required additional cross-linking with an anti-mouse Fab'gamma. These results indicate that each type of receptor can transduce signals to the cell independently. Bispecific antibodies (anti-Fc-gamma-R x anti-target) linking cytotoxic Fc-gamma-R-bearing effector cells to tumour target cells also mediated increases in [Ca2+]i for all Fc-gamma-R tested except for Fc-gamma-RIII on granulocytes. The failure to transduce a signal via this receptor may be related to the GPI link, which is in contrast to the transmembrane link of Fc-gamma-RIII on NK cells. Significant lysis of tumour cell targets occurred when bispecific antibodies recruited NK cells or monocytes, but not granulocytes, via Fc-gamma-R. Chelation of intracellular Ca2+ in the effector cells reduced the observed lysis, suggesting a role for Ca2+ in the pathways leading to cytotoxicity.