The β subunit of the type I Fcε receptor is a target for peptides inhibiting IgE-mediated secretory response of mast cells

被引:21
作者
Andrásfalvy, M
Péterfy, H
Tóth, G
Matkó, J
Abramson, J
Kerekes, K
Vámosi, G
Pecht, I
Erdei, A
机构
[1] Eotvos Lorand Univ, Dept Immunol, H-1117 Budapest, Hungary
[2] Eotvos Lorand Univ, Hungarian Acad Sci, Immunol Res Grp, H-1117 Budapest, Hungary
[3] Univ Szeged, Dept Med Chem, H-6720 Szeged, Hungary
[4] Univ Debrecen, Hungarian Acad Sci, Cell Biophys Res Grp, H-4012 Debrecen, Hungary
[5] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel
关键词
D O I
10.4049/jimmunol.175.5.2801
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Peptides originally derived from complement component C3a were earlier shown to inhibit the type I Fc epsilon R (Fc epsilon RI)-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 Fc epsilon RI-induced membrane proximal events, suppress phosphorylation of the Fc epsilon RI beta 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-alpha secretion. Experiments using two independent methods provided evidence that the interaction site of complement-derived peptides is the Fc epsilon RI beta-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.
引用
收藏
页码:2801 / 2806
页数:6
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