Activation of human neutrophils by soluble immune complexes: Role of FcγRII and FcγRIIIb in stimulation of the respiratory burst and elevation of intracellular Ca2+

Abstract

Activation of control, unprimed neutrophils with soluble immune complexes fails to generate a respiratory burst. However, if the cells are primed with either tumor necrosis factor-α or granulocyte-macrophage colony-stimulating factor prior to addition of soluble immune complexes, then a rapid and transient burst of reactive oxidant secretion is observed. In unprimed neutrophils the soluble immune complexes stimulate an intracellular Ca2+ transient that arises from the mobilization of intracellular Ca2+. However, in primed cells, an 'extra' intracellular Ca2+ signal is observed that arises from Ca2+ influx. After removal of FcγRIIIb by treatment with pronase or PI-PLC, the soluble immune complexes fail to activate a respiratory burst in unprimed neutrophils and the 'extra' Ca2+ signal is not observed. These results indicate that during priming FcγRIIIb becomes functionally activated and thence its ligation leads to stimulated Ca2+ influx and the generation of intracellular signals that lead to NADPH oxidase activation. Experiments using Fab/F(ab')2 fragments to specifically crosslink either FcγRII or FcγRIIIb and experiments with neutrophils from an individual with FcγRIIIb gene deficiency confirm this important function for FcγRIIIb in neutrophil activation.