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.