Basophil signalling in IgE-mediated basophil degranulation
Crosslinking of IgE presented on FcεRI, the high affinity IgE receptor
on blood basophils, results in increased phosphorylation of ITAMs of the
FcεRI𝛽𝛾 subunits, and of the SH2-domains of kinases Syk and
Lyn12, which are under constant counter-regulation by
dephosphorylation through CD4513. Net phosphorylation
of FceRI𝛽𝛾 and Syk leads to massive amplification of the initial signal,
similar to that of neuronal signalling, and regulated exocytosis of
secretory lysosomes that stain with basic dyes as they contain
histamine, histidine decarboxylase, heparin and
proteases14. Immune-regulated exocytosis uses SNAP23
and VAMP8 whereas SNAP25 and VAMP1 and VAMP2 are used in neuronal
signalling15. Degranulation has been studied mainly in
murine mast cells and the RBL cell line, as these can be cultured in
sufficient quantities16. IgE-mediated activation is an
example of a bi- or multivalent activation mechanism through adaptive
immune signalling. Use of wortmannin sensitive kinases PI3K and MAPK can
confirm the IgE-mediated origin of the activating
signal1,17, since wortmannin can thus inhibit the IgE
pathway. The fusion of secretory lysosomes with the cell membrane in
basophil and mast cells may also be activated through G-coupled protein
receptors linked to receptors for univalent exogenous substances like
fMLP and ligands for MRGPRX218, and may be modulated
by receptors for endogenous univalent substances like PAF, IL8 and
C5a14.