Regulation of high-affinity IgE receptor-mediated mast cell activation by murine low-affinity IgG receptors.
Allergic symptoms result from the release of granular and lipidic mediators and of cytokines by inflammatory cells. The whole process is initiated by the aggregation of mast cell and basophil high-affinity IgE receptors (Fc epsilon RI) by IgE and antigen. We report here that IgE-induced release of mediator and cytokine can be inhibited by cross-linking Fc epsilon RI to low-affinity IgG receptors (Fc gamma RII) which are constitutively expressed on mast cells and basophils. Using a model of stable transfectants in RBL-2H3 cells expressing endogeneous rat Fc epsilon RI and recombinant murine Fc gamma RII, we showed that inhibition requires that Fc epsilon RI be crosslinked to Fc gamma RII by the same multivalent ligand. Inhibition of cross-linked receptors left non-cross-linked Fc epsilon RI capable of triggering mediator release and was reversible upon disengagement. Both isoforms of wild-type Fc gamma RII were equally capable of inhibiting Fc epsilon RI-mediated mast cell activation provided they had an intact intracytoplasmic domain. Our results demonstrate that mast cell secretory responses triggered by high-affinity receptors for IgE may be controlled by low-affinity receptors for IgG. This regulation of Fc epsilon RI-mediated mast cell activation is of potential interest in mast cell physiology and in allergic pathology.
Daëron
M
M
Laboratoire d'Immunologie Cellulaire et Clinique, INSERM U255, Institut Curie, Paris, France.
Malbec
O
O
Latour
S
S
Arock
M
M
Fridman
W H
WH
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002460:Cell Line; D002478:Cells, Cultured; D018076:DNA, Complementary; D005455:Fluorescent Antibody Technique; D007073:Immunoglobulin E / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D007700:Kinetics; D008407:Mast Cells / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017455:Receptors, IgE / Q000096:biosynthesis / Q000502:physiology*; D017452:Receptors, IgG / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D012701:Serotonin / Q000378:metabolism; D014162:Transfection
D018076:DNA, Complementary; D007074:Immunoglobulin G; D017455:Receptors, IgE; D017452:Receptors, IgG; D011994:Recombinant Proteins; D012701:Serotonin; D007073:Immunoglobulin E