Figure legend
Figure 1. Pathophysiology of IgE-mediated mast cell activation and of post-anaphylaxis mast cell anergy. Adapted from Mohamed et al.11
IgE-dependent mast cell activation (blue labeling). Upon antigen cross-linking of the IgE/FcεRI complex, β and ɣ chains of the receptor aggregate and their immunoreceptor tyrosine-based activation motifs (ITAM) are phosphorylated by Lyn, which also activates Syk. This leads to a cascade involving numerous intermediates such as PI3K, PLC- ɣ and PKC. The influx of extracellular calcium (Ca2+) leads to mast cell degranulation, internalization of the Ag/IgE/FceRI complexes and cytoskeletal movements. ITAM phosphorylation is also involved in the activation of MAPK, resulting in eicosanoid synthesis and cytokine gene transcription.
Post-anaphylactic mast cell anergy (orange labeling) . Massive degranulation can lead to depletion of mast cell mediators, requiring a period for synthesis and regranulation. It is possible that Lyn can activate inhibitory molecules such as SHIP-1, a phosphatase inhibiting the mast cell response via the PI3K pathway. The internalization of antigen-IgE-FcεRI complexes can further reduce the number of FcεRIs available at the cell surface, impairing mast cell activation; while β-adrenergic receptor agonists can block mast cell degranulation via an inhibitory action on PKC. There is no proof that anergy is not a universal phenomenon.
Ag= Antigen; Fc εRI= high-affinity receptor for IgE ; ITAM= immunoreceptor tyrosine-based activation motif; Lyn= member of the Src family of protein tyrosine kinases ; MAPK= mitogen-activated protein kinase ; P= phosphorylation; PI3K= phosphoinositide 3-kinase ; PKC= protein kinase C ; PLC-ɣ = phospholipase C-ɣ ; SHIP 1= Src homology 2-containing inositol polyphosphate-5’-phosphatase 1 ; Syk= spleen-associated tyrosine kinase.