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Akira Matsuda, Yoshimichi Okayama, Nobuyuki Ebihara, Norihiko Yokoi, Akira Murakami; Intracellular Introduction of Phosphorylated FcRIβ-ITAM Activation Motif Inhibit Mast Cell Degranulation In Ex Vivo Giant Papillae Tissue. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1125.
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© ARVO (1962-2015); The Authors (2016-present)
Human high affinity IgE receptor beta (FcεRIβ) was reported to function as an amplifier of FcεRIβ expression and FcεRI-mediated activation signals. We previously reported that the ratio of FcεRIβ+ cells number to the mast cell number was increased in the giant papillae obtained from chronic allergic conjunctivitis patients (IOVS 50:2871-7). To clarify the role of FcεRIβ in chronic allergic conjunctivitis, we tried to inhibit FcεRIβ signaling cascades in mast cell.
FcεRIβ expression in cultured human mast cells was reduced by a lentiviral shRNA silencing technique. Recombinant cell-penetrating forms of phosphorylated FcεRIβ immunoreceptor tyrosine-based activation motif (ITAM) peptides were developed for intracellular delivery to disturb the interaction between Lyn and phosphorylated endogenous FcεRIβ ITAM. The peptides were reacted with human cultured mast cells and histamine release assay was carried out. 1mm-square tissue blocks were excised from three giant papillae tissue samples. After 30min incubation with 2µM of the peptide, IgE-crosslinking was carried out by anti-IgE antibody. Histamine release ratio was examined by EIA assay.
The diminution of FcεRIβ by shRNA significantly down-regulated IgE-dependent degranulation, PGD2 and IL-8 production. The phospho-ITAM peptide was localized in cytoplasm and captured Lyn in human mast cells. The peptide significantly inhibited IgE-dependent histamine release and PGD2 synthesis. The administration of the peptide to giant papillae specimens ex vivo inhibited IgE-dependent histamine release. [The ratio of the released histamine was 5.6±3.7% (phospho-ITAM peptide), and was 29.3±2.1% (control non-phospho-ITAM peptide). ]
The phospho-FcεRIβ ITAM peptide may be potentially useful for the treatment of chronic allergic conjunctivitis.
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