Heterotypic FcR Clusters Evoke a Synergistic Ca Response in Human Neutrophils

• Published in: The Journal of biological chemistry 1995-05, Vol.270 (18), p.10671
• Main Authors: Paula J. M. Vossebeld, Jan Kessler, Albert E. G. Kr. von dem Borne, Dirk Roos, Arthur J. Verhoeven
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.18.10671

Both Fc receptors on human neutrophils (Fc RIIa and Fc RIIIb) are capable of initiating signal transduction after multivalent cross-linking. However, immune complexes most likely activate neutrophils by a combined homotypic and heterotypic cross-linking of Fc Rs. We have investigated the effect of homotypic and heterotypic Fc R cluster formation on changes in the intracellular free Ca concentration. Combined heterotypic and homotypic cluster formation resulted in a Ca response that was strongly enhanced as compared to the sum of both individual Fc R responses. This synergistic response was caused by the formation of heterotypic clusters of Fc Rs and not by the simultaneous formation of homotypic clusters. This conclusion was supported by experiments with a bispecific antibody binding to both Fc RIIa and Fc RIIIb. The heterotypic Fc R cross-linking results in efficient activation of Ca influx, probably caused by a more pronounced depletion of intracellular Ca stores. Stimulation with immune complexes also induced Ca influx in normal neutrophils, but not in Fc RIIIb-deficient neutrophils. The synergism between both Fc Rs was also apparent in other responses of neutrophils, such as the activation of the respiratory burst. This study shows that the two different Fc Rs on neutrophils complement each other in mediating an important cellular response.