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Both Fc
Volume 270,
Number 18,
Issue of May 5, pp. 10671-10679, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
R Clusters Evoke a Synergistic Ca
Response in
Human Neutrophils
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.
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