Molecular consequences of human mast cell activation following immunoglobulin E–high-affinity immunoglobulin E receptor (IgE–FcϵRI) interaction

• Published in: Biochemical pharmacology 1999-12, Vol.58 (12), p.1841-1850
• Main Authors: Reischl, Ilona G, Coward, William R, Church, Martin K
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; FcϵRI; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; IgE; Immediate hypersensitivity. Allergy. Anaphylaxis, etc; Immunobiology; Immunoglobulin E - immunology; inositol phosphate; Inositol Phosphates - metabolism; MAP kinase; mast cell; Mast Cells - enzymology; Mast Cells - immunology; Mast Cells - metabolism; Mitogen-Activated Protein Kinases - metabolism; Reaction mechanisms, antibodies, chemical mediators; Receptors, IgE - biosynthesis; Receptors, IgE - immunology; Receptors, IgE - metabolism; Signal Transduction; sphingosine
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(99)00226-9

The cross-linking by immunoglobulin E of its high-affinity receptor, FcϵRI, on mast cells initiates a complex series of biochemical events leading to degranulation and the synthesis and secretion of eicosanoids and cytokines through the action of transcription factors, such as nuclear factor-κB. The initial activation involves the phosphorylation of FcϵRI β- and γ-subunits through the actions of the tyrosine kinases lyn and syk. For the purposes of description, the subsequent events may be grouped in three cascades characterized by the key proteins involved. First, the phospholipase C–inositol phosphate cascade activates protein kinase C and is largely responsible for calcium mobilization and influx. Second, activation of Ras and Raf via mitogen-activated protein kinase causes the production of arachidonic acid metabolites. Third, the generation of sphingosine and sphingosine-1-phosphate occurs through activation of sphingomyelinase. While the early signaling events tend to be specific for the cited cascades, there is an increasing overlap of activated proteins with the downstream propagation of the signal. It is the balanced interaction between these proteins that culminates in degranulation, synthesis, and release of eicosanoids and cytokines.