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Granulocyte-macrophage colony-stimulating factor induces sequential
activation and deactivation of binding via a low-affinity IgG Fc receptor,
hFc gamma RII, on human eosinophils
L Koenderman, SW Hermans, PJ Capel and JG van de Winkel
Department of Pulmonary Diseases, University Hospital Utrecht, The
Netherlands.
Eosinophils are important in antibody-mediated immune defense against
parasites based on interaction with Ig receptors (FcR). Of the three
classes of IgG FcR in humans, hFc gamma RI, II, and III, solely hFc gamma
RII (CD32) is expressed on freshly isolated eosinophils. Despite an
expression level similar to that found on monocytes and polymorphonuclear
granulocytes, binding activity of hFc gamma RII on eosinophils is
constitutively low. Freshly isolated eosinophils had a negligible ability
to form rosettes with IgG-sensitized erythrocytes (EA-IgG). Addition of
granulocyte-macrophage colony-stimulating factor (GM-CSF) caused an
approximately threefold increase in EA-IgG rosettes. This increase was
maximal after 35 minutes, and declined upon further incubation at 37
degrees C. Analysis of hFc gamma RII expression levels showed no
significant changes and neither was the expression of other hFc gamma R
classes induced. Blocking studies with anti-Fc gamma receptor monoclonal
antibody (MoAb) proved hFc gamma RII specificity of enhanced IgG complex
binding. These phenomena were not restricted to GM- CSF action, because the
addition of interleukin-3 or interleukin-5 similarly enhanced EA-IgG
binding. The kinetics of activation of hFc gamma RII binding activity were
paralleled by the binding of EA-C3bi to CR3 on eosinophils. In contrast to
the stable expression of hFc gamma RII during activation with GM-CSF, CR3
expression increased slowly. Ligand binding via both types of opsonin
receptors proved receptor specific. However, the kinetics of enhanced
binding via hFc gamma RII and CR3 suggested the possibility of a common
mechanism underlying the enhancement of ligand binding via hFc gamma RII
and CR3. This hypothesis was supported by the fact that binding via hFc
gamma RII proved sensitive to both high concentrations of F(ab')2 fragments
of anti-CD11b MoAb MO1 and chelation of bivalent cations with EDTA. In
conclusion, our studies indicate that cytokines can induce a transient
enhancement of hFc gamma RII binding activity. Qualitative, and not
quantitative, changes in this receptor appear to underly the modulation of
binding activity, which may be linked to changes in CR3 activity.
Volume 81,
Issue 9,
pp. 2413-2419,
05/01/1993
Copyright © 1993 by The American Society of Hematology

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