Coaggregation of FcepsilonRI with FcgammaRIIB Inhibits Degranulation but Not Induction of Bcl-2 Family Members A1 and Bim in Mast Cells.
: The aggregation of high-affinity immunoglobulin E (IgE) receptors (FcepsilonRI) on mast cells is a critical event in the initiation of an allergic reaction. Coengagement of FcepsilonRI with immunoglobulin G (IgG) low-affinity receptor FcgammaRIIB/CD32 inhibits degranulation and the release of inflammatory mediators from mast cells and has therefore been proposed as a new therapeutic approach for the treatment of allergies. In this study, we investigated whether FcgammaRIIB, besides inhibiting degranulation, negatively regulates other signalling pathways downstream of FcepsilonRI. For this, we determined the phosphorylation and/or expression of proteins involved in the regulation of mast-cell apoptosis. Coaggregation led to an attenuation of Akt phosphorylation but did not inhibit phosphorylation of transcription factor Foxo3a or its proapoptotic target, Bim. Similarly, FcepsilonRI-dependent expression of the prosurvival gene A1 was not affected by coaggregation. Our data demonstrate that coengagement of FcepsilonRI and FcgammaRIIB inhibits degranulation but not the signalling pathways regulating Bcl-2 family members Bim and A1.
Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet, Stockholm, Sweden.
Maria
M
Ekoff
Christine
C
Möller
Zou
Z
Xiang
Gunnar
G
Nilsson