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Márton Andrásfalvy, Hajna Péterfy, Gábor Tóth, János Matkó, Jakub Abramson, Krisztina Kerekes, György Vámosi, Israel Pecht, Anna Erdei, The β Subunit of the Type I Fcε Receptor Is a Target for Peptides Inhibiting IgE-Mediated Secretory Response of Mast Cells, The Journal of Immunology, Volume 175, Issue 5, September 2005, Pages 2801–2806, https://doi.org/10.4049/jimmunol.175.5.2801
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Abstract
Peptides originally derived from complement component C3a were earlier shown to inhibit the type I FcεR (FcεRI)-mediated degranulation of mucosal type mast cells. In the present study, we show that C3a7, a peptide with a natural sequence, and its modified derivative, C3a9, are powerful inhibitors of the above response of both serosal and mucosal type mastocytes. We demonstrate that these peptides inhibit FcεRI-induced membrane proximal events, suppress phosphorylation of the FcεRI β subunit, the protein tyrosine kinase Lyn, as well as the transient rise in free cytosolic Ca2+ level. The late phase of cellular response was also inhibited, as demonstrated by the reduced TNF-α secretion. Experiments using two independent methods provided evidence that the interaction site of complement-derived peptides is the FcεRI β-chain. This was further supported by fluorescence confocal microscopic colocalization and resonance energy transfer measurements. Taken together, these results suggest the presence of distinct “activating” and “inhibitory” motifs in the C3a sequence. Response to both is in balance under physiologic conditions. Furthermore, present data predict that such inhibitory peptides may serve as potent agents for future therapeutic intervention.
